Skip to main content
Top
Published in: Endocrine Pathology 2/2014

01-06-2014

Unraveling Tumor Grading and Genomic Landscape in Lung Neuroendocrine Tumors

Authors: Giuseppe Pelosi, Mauro Papotti, Guido Rindi, Aldo Scarpa

Published in: Endocrine Pathology | Issue 2/2014

Login to get access

Abstract

Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer. When applied to single genes, panels of genes, exome, or the whole genome by using either frozen or paraffin tissues, NGS techniques increase our understanding of cancer, thus realizing the bases of precision medicine. Data are emerging that TC and AC are mainly altered in chromatin remodeling genes, whereas LCNEC and SCLC are also mutated in cell cycle checkpoint and cell differentiation regulators. A common denominator to all lung NETs is a deregulation of cell proliferation, which represents a biological rationale for morphologic (mitoses and necrosis) and molecular (Ki-67 antigen) parameters to successfully serve as predictors of tumor behavior (i.e., identification of pathological entities with clinical correlation). It is envisaged that a novel grading system in lung NETs based on the combined assessment of mitoses, necrosis, and Ki-67 LI may offer a better stratification of prognostic classes, realizing a bridge between molecular alterations, morphological features, and clinical behavior.
Literature
1.
go back to reference Travis W, Brambilla E, Muller-Hermelink H, Harris C (2004) Tumours of the lung, pleura, thymus and heart. IARC Press, Lyon. Travis W, Brambilla E, Muller-Hermelink H, Harris C (2004) Tumours of the lung, pleura, thymus and heart. IARC Press, Lyon.
2.
go back to reference Franks TJ, Galvin JR (2008) Lung tumors with neuroendocrine morphology: essential radiologic and pathologic features. Arch Pathol Lab Med 132: 1055–1061.PubMed Franks TJ, Galvin JR (2008) Lung tumors with neuroendocrine morphology: essential radiologic and pathologic features. Arch Pathol Lab Med 132: 1055–1061.PubMed
3.
go back to reference Travis WD, Rush W, Flieder DB, Falk R, Fleming MV, Gal AA, Koss MN (1998) Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 22: 934–944.PubMed Travis WD, Rush W, Flieder DB, Falk R, Fleming MV, Gal AA, Koss MN (1998) Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 22: 934–944.PubMed
4.
go back to reference Travis WD, Linnoila RI, Tsokos MG, Hitchcock CL, Cutler GB, Jr., Nieman L, Chrousos G, Pass H, Doppman J (1991) Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 15: 529–553.PubMed Travis WD, Linnoila RI, Tsokos MG, Hitchcock CL, Cutler GB, Jr., Nieman L, Chrousos G, Pass H, Doppman J (1991) Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 15: 529–553.PubMed
5.
go back to reference Asamura H, Kameya T, Matsuno Y, Noguchi M, Tada H, Ishikawa Y, Yokose T, Jiang SX, Inoue T, Nakagawa K, Tajima K, Nagai K (2006) Neuroendocrine neoplasms of the lung: a prognostic spectrum. J Clin Oncol 24: 70–76.PubMed Asamura H, Kameya T, Matsuno Y, Noguchi M, Tada H, Ishikawa Y, Yokose T, Jiang SX, Inoue T, Nakagawa K, Tajima K, Nagai K (2006) Neuroendocrine neoplasms of the lung: a prognostic spectrum. J Clin Oncol 24: 70–76.PubMed
6.
go back to reference Righi L, Volante M, Tavaglione V, Bille A, Daniele L, Angusti T, Inzani F, Pelosi G, Rindi G, Papotti M (2010) Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 ‘clinically aggressive’ cases. Ann Oncol 21: 548–555.PubMed Righi L, Volante M, Tavaglione V, Bille A, Daniele L, Angusti T, Inzani F, Pelosi G, Rindi G, Papotti M (2010) Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 ‘clinically aggressive’ cases. Ann Oncol 21: 548–555.PubMed
7.
go back to reference Rindi G, Klersy C, Inzani F, Fellegara G, Ampollini L, Ardizzoni A, Campanini N, Carbognani P, De Pas TM, Galetta D, Granone PL, Righi L, Rusca M, Spaggiari L, Tiseo M, Viale G, Volante M, Papotti M, Pelosi G (2014) Grading the neuroendocrine tumors of the lung: an evidence-based proposal. Endocr Relat Cancer 21: 1–16.PubMed Rindi G, Klersy C, Inzani F, Fellegara G, Ampollini L, Ardizzoni A, Campanini N, Carbognani P, De Pas TM, Galetta D, Granone PL, Righi L, Rusca M, Spaggiari L, Tiseo M, Viale G, Volante M, Papotti M, Pelosi G (2014) Grading the neuroendocrine tumors of the lung: an evidence-based proposal. Endocr Relat Cancer 21: 1–16.PubMed
8.
go back to reference Gridelli C, Rossi A, Airoma G, Bianco R, Costanzo R, Daniele B, Chiara GD, Grimaldi G, Irtelli L, Maione P, Morabito A, Piantedosi FV, Riccardi F (2013) Treatment of pulmonary neuroendocrine tumours: State of the art and future developments. Cancer Treat Rev 39: 466–472.PubMed Gridelli C, Rossi A, Airoma G, Bianco R, Costanzo R, Daniele B, Chiara GD, Grimaldi G, Irtelli L, Maione P, Morabito A, Piantedosi FV, Riccardi F (2013) Treatment of pulmonary neuroendocrine tumours: State of the art and future developments. Cancer Treat Rev 39: 466–472.PubMed
9.
go back to reference Beasley MB, Thunnissen FB, Brambilla E, Hasleton P, Steele R, Hammar SP, Colby TV, Sheppard M, Shimosato Y, Koss MN, Falk R, Travis WD (2000) Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol 31: 1255–1265.PubMed Beasley MB, Thunnissen FB, Brambilla E, Hasleton P, Steele R, Hammar SP, Colby TV, Sheppard M, Shimosato Y, Koss MN, Falk R, Travis WD (2000) Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol 31: 1255–1265.PubMed
10.
go back to reference Filosso PL, Rena O, Donati G, Casadio C, Ruffini E, Papalia E, Oliaro A, Maggi G (2002) Bronchial carcinoid tumors: surgical management and long-term outcome. J Thorac Cardiovasc Surg 123: 303–309.PubMed Filosso PL, Rena O, Donati G, Casadio C, Ruffini E, Papalia E, Oliaro A, Maggi G (2002) Bronchial carcinoid tumors: surgical management and long-term outcome. J Thorac Cardiovasc Surg 123: 303–309.PubMed
11.
go back to reference Filosso PL, Ruffini E, Di Gangi S, Guerrera F, Bora G, Ciccone G, Galassi C, Solidoro P, Lyberis P, Oliaro A, Sandri A (2013) Prognostic factors in neuroendocrine tumours of the lung: a single-centre experience. Eur J Cardiothorac Surg 45:521–526.PubMed Filosso PL, Ruffini E, Di Gangi S, Guerrera F, Bora G, Ciccone G, Galassi C, Solidoro P, Lyberis P, Oliaro A, Sandri A (2013) Prognostic factors in neuroendocrine tumours of the lung: a single-centre experience. Eur J Cardiothorac Surg 45:521–526.PubMed
12.
go back to reference Garcia-Yuste M, Matilla JM, Alvarez-Gago T, Duque JL, Heras F, Cerezal LJ, Ramos G (2000) Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study. Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR). Ann Thorac Surg 70: 258–263.PubMed Garcia-Yuste M, Matilla JM, Alvarez-Gago T, Duque JL, Heras F, Cerezal LJ, Ramos G (2000) Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study. Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR). Ann Thorac Surg 70: 258–263.PubMed
13.
go back to reference Garcia-Yuste M, Matilla JM, Cueto A, Paniagua JM, Ramos G, Canizares MA, Muguruza I (2007) Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung. Eur J Cardiothorac Surg 31: 192–197.PubMed Garcia-Yuste M, Matilla JM, Cueto A, Paniagua JM, Ramos G, Canizares MA, Muguruza I (2007) Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung. Eur J Cardiothorac Surg 31: 192–197.PubMed
14.
go back to reference den Bakker MA, Willemsen S, Grunberg K, Noorduijn LA, van Oosterhout MF, van Suylen RJ, Timens W, Vrugt B, Wiersma-van Tilburg A, Thunnissen FB (2010) Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability. Histopathology 56: 356–363. den Bakker MA, Willemsen S, Grunberg K, Noorduijn LA, van Oosterhout MF, van Suylen RJ, Timens W, Vrugt B, Wiersma-van Tilburg A, Thunnissen FB (2010) Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability. Histopathology 56: 356–363.
15.
go back to reference Ha SY, Han J, Kim WS, Suh BS, Roh MS (2012) Interobserver variability in diagnosing high-grade neuroendocrine carcinoma of the lung and comparing it with the morphometric analysis. Korean J Pathol 46: 42–47.PubMedCentralPubMed Ha SY, Han J, Kim WS, Suh BS, Roh MS (2012) Interobserver variability in diagnosing high-grade neuroendocrine carcinoma of the lung and comparing it with the morphometric analysis. Korean J Pathol 46: 42–47.PubMedCentralPubMed
16.
go back to reference Iyoda A, Hiroshima K, Nakatani Y, Fujisawa T (2007) Pulmonary large cell neuroendocrine carcinoma: its place in the spectrum of pulmonary carcinoma. Ann Thorac Surg 84: 702–707.PubMed Iyoda A, Hiroshima K, Nakatani Y, Fujisawa T (2007) Pulmonary large cell neuroendocrine carcinoma: its place in the spectrum of pulmonary carcinoma. Ann Thorac Surg 84: 702–707.PubMed
17.
go back to reference Marchevsky AM, Gal AA, Shah S, Koss MN (2001) Morphometry confirms the presence of considerable nuclear size overlap between “small cells” and “large cells” in high-grade pulmonary neuroendocrine neoplasms. Am J Clin Pathol 116: 466–472.PubMed Marchevsky AM, Gal AA, Shah S, Koss MN (2001) Morphometry confirms the presence of considerable nuclear size overlap between “small cells” and “large cells” in high-grade pulmonary neuroendocrine neoplasms. Am J Clin Pathol 116: 466–472.PubMed
18.
go back to reference Huang Q, Muzitansky A, Mark EJ (2002) Pulmonary neuroendocrine carcinomas. A review of 234 cases and a statistical analysis of 50 cases treated at one institution using a simple clinicopathologic classification. Arch Pathol Lab Med 126: 545–553.PubMed Huang Q, Muzitansky A, Mark EJ (2002) Pulmonary neuroendocrine carcinomas. A review of 234 cases and a statistical analysis of 50 cases treated at one institution using a simple clinicopathologic classification. Arch Pathol Lab Med 126: 545–553.PubMed
19.
go back to reference Moran CA, Suster S, Coppola D, Wick MR (2009) Neuroendocrine carcinomas of the lung: a critical analysis. Am J Clin Pathol 131: 206–221.PubMed Moran CA, Suster S, Coppola D, Wick MR (2009) Neuroendocrine carcinomas of the lung: a critical analysis. Am J Clin Pathol 131: 206–221.PubMed
20.
go back to reference Axiotis C. The neuroendocrine lung. In: Li Volsi V, Asa S, editors. Endocrine Pathology. New York Edinburgh: Churchill Livingstone; 2002. p. 261–296. Axiotis C. The neuroendocrine lung. In: Li Volsi V, Asa S, editors. Endocrine Pathology. New York Edinburgh: Churchill Livingstone; 2002. p. 261–296.
21.
go back to reference Travis WD, Gal AA, Colby TV, Klimstra DS, Falk R, Koss MN (1998) Reproducibility of neuroendocrine lung tumor classification. Hum Pathol 29: 272–279.PubMed Travis WD, Gal AA, Colby TV, Klimstra DS, Falk R, Koss MN (1998) Reproducibility of neuroendocrine lung tumor classification. Hum Pathol 29: 272–279.PubMed
22.
go back to reference Veronesi G, Morandi U, Alloisio M, Terzi A, Cardillo G, Filosso P, Rea F, Facciolo F, Pelosi G, Gandini S, Calabro F, Casali C, Marulli G, Spaggiari L (2006) Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer 53: 111–115.PubMed Veronesi G, Morandi U, Alloisio M, Terzi A, Cardillo G, Filosso P, Rea F, Facciolo F, Pelosi G, Gandini S, Calabro F, Casali C, Marulli G, Spaggiari L (2006) Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer 53: 111–115.PubMed
23.
go back to reference Grand B, Cazes A, Mordant P, Foucault C, Dujon A, Guillevin EF, Barthes Fle P, Riquet M (2013) High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications. Lung Cancer 81: 404–409.PubMed Grand B, Cazes A, Mordant P, Foucault C, Dujon A, Guillevin EF, Barthes Fle P, Riquet M (2013) High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications. Lung Cancer 81: 404–409.PubMed
24.
go back to reference Niemiec J, Adamczyk A, Malecki K, Ambicka A, Rys J (2013) Tumor grade and matrix metalloproteinase 2 expression in stromal fibroblasts help to stratify the high-risk group of patients with early breast cancer identified on the basis of st Gallen recommendations. Clin Breast Cancer 13: 119–128.PubMed Niemiec J, Adamczyk A, Malecki K, Ambicka A, Rys J (2013) Tumor grade and matrix metalloproteinase 2 expression in stromal fibroblasts help to stratify the high-risk group of patients with early breast cancer identified on the basis of st Gallen recommendations. Clin Breast Cancer 13: 119–128.PubMed
25.
go back to reference Zumsteg ZS, Spratt DE, Pei I, Zhang Z, Yamada Y, Kollmeier M, Zelefsky MJ (2013) A new risk classification system for therapeutic decision making with intermediate-risk prostate cancer patients undergoing dose-escalated external-beam radiation therapy. Eur Urol 64: 895–902.PubMed Zumsteg ZS, Spratt DE, Pei I, Zhang Z, Yamada Y, Kollmeier M, Zelefsky MJ (2013) A new risk classification system for therapeutic decision making with intermediate-risk prostate cancer patients undergoing dose-escalated external-beam radiation therapy. Eur Urol 64: 895–902.PubMed
26.
go back to reference Procopio G, Verzoni E, Iacovelli R, Biasoni D, Testa I, Porcu L, De Braud F (2012) Prognostic factors for survival in patients with metastatic renal cell carcinoma treated with targeted therapies. Br J Cancer 107: 1227–1232.PubMedCentralPubMed Procopio G, Verzoni E, Iacovelli R, Biasoni D, Testa I, Porcu L, De Braud F (2012) Prognostic factors for survival in patients with metastatic renal cell carcinoma treated with targeted therapies. Br J Cancer 107: 1227–1232.PubMedCentralPubMed
27.
go back to reference Ueno H, Hase K, Hashiguchi Y, Shimazaki H, Tanaka M, Miyake O, Masaki T, Shimada Y, Kinugasa Y, Mori Y, Kishimoto M, Kameoka S, Sato Y, Matsuda K, Nakadoi K, Shinto E, Nakamura T, Sugihara K (2014) Site-specific Tumor Grading System in Colorectal Cancer: Multicenter Pathologic Review of the Value of Quantifying Poorly Differentiated Clusters. Am J Surg Pathol 38: 197–204.PubMed Ueno H, Hase K, Hashiguchi Y, Shimazaki H, Tanaka M, Miyake O, Masaki T, Shimada Y, Kinugasa Y, Mori Y, Kishimoto M, Kameoka S, Sato Y, Matsuda K, Nakadoi K, Shinto E, Nakamura T, Sugihara K (2014) Site-specific Tumor Grading System in Colorectal Cancer: Multicenter Pathologic Review of the Value of Quantifying Poorly Differentiated Clusters. Am J Surg Pathol 38: 197–204.PubMed
28.
go back to reference Capelle L, Fontaine D, Mandonnet E, Taillandier L, Golmard JL, Bauchet L, Pallud J, Peruzzi P, Baron MH, Kujas M, Guyotat J, Guillevin R, Frenay M, Taillibert S, Colin P, Rigau V, Vandenbos F, Pinelli C, Duffau H (2013) Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases: clinical article. J Neurosurg 118: 1157–1168.PubMed Capelle L, Fontaine D, Mandonnet E, Taillandier L, Golmard JL, Bauchet L, Pallud J, Peruzzi P, Baron MH, Kujas M, Guyotat J, Guillevin R, Frenay M, Taillibert S, Colin P, Rigau V, Vandenbos F, Pinelli C, Duffau H (2013) Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases: clinical article. J Neurosurg 118: 1157–1168.PubMed
29.
go back to reference Travis WD1, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D (2011) International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: 244–285PubMed Travis WD1, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D (2011) International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: 244–285PubMed
30.
go back to reference Kadota K, Suzuki K, Kachala SS, Zabor EC, Sima CS, Moreira AL, Yoshizawa A, Riely GJ, Rusch VW, Adusumilli PS, Travis WD (2012) A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma. Mod Pathol 25: 1117–1127.PubMed Kadota K, Suzuki K, Kachala SS, Zabor EC, Sima CS, Moreira AL, Yoshizawa A, Riely GJ, Rusch VW, Adusumilli PS, Travis WD (2012) A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma. Mod Pathol 25: 1117–1127.PubMed
31.
go back to reference Sica G, Yoshizawa A, Sima CS, Azzoli CG, Downey RJ, Rusch VW, Travis WD, Moreira AL (2010) A grading system of lung adenocarcinomas based on histologic pattern is predictive of disease recurrence in stage I tumors. Am J Surg Pathol 34: 1155–1162.PubMed Sica G, Yoshizawa A, Sima CS, Azzoli CG, Downey RJ, Rusch VW, Travis WD, Moreira AL (2010) A grading system of lung adenocarcinomas based on histologic pattern is predictive of disease recurrence in stage I tumors. Am J Surg Pathol 34: 1155–1162.PubMed
32.
go back to reference von der Thusen JH, Tham YS, Pattenden H, Rice A, Dusmet M, Lim E, Nicholson AG (2013) Prognostic significance of predominant histologic pattern and nuclear grade in resected adenocarcinoma of the lung: potential parameters for a grading system. J Thorac Oncol 8: 37–44.PubMed von der Thusen JH, Tham YS, Pattenden H, Rice A, Dusmet M, Lim E, Nicholson AG (2013) Prognostic significance of predominant histologic pattern and nuclear grade in resected adenocarcinoma of the lung: potential parameters for a grading system. J Thorac Oncol 8: 37–44.PubMed
33.
go back to reference Kadota K, Colovos C, Suzuki K, Rizk NP, Dunphy MP, Zabor EC, Sima CS, Yoshizawa A, Travis WD, Rusch VW, Adusumilli PS (2012) FDG-PET SUVmax combined with IASLC/ATS/ERS histologic classification improves the prognostic stratification of patients with stage I lung adenocarcinoma. Ann Surg Oncol 19: 3598–3605.PubMedCentralPubMed Kadota K, Colovos C, Suzuki K, Rizk NP, Dunphy MP, Zabor EC, Sima CS, Yoshizawa A, Travis WD, Rusch VW, Adusumilli PS (2012) FDG-PET SUVmax combined with IASLC/ATS/ERS histologic classification improves the prognostic stratification of patients with stage I lung adenocarcinoma. Ann Surg Oncol 19: 3598–3605.PubMedCentralPubMed
34.
go back to reference Cerilli LA, Ritter JH, Mills SE, Wick MR (2001) Neuroendocrine neoplasms of the lung. Am J Clin Pathol 116 Suppl: S65-96.PubMed Cerilli LA, Ritter JH, Mills SE, Wick MR (2001) Neuroendocrine neoplasms of the lung. Am J Clin Pathol 116 Suppl: S65-96.PubMed
35.
go back to reference Wick MR (2000) Neuroendocrine neoplasia. Current concepts. Am J Clin Pathol 113: 331–335.PubMed Wick MR (2000) Neuroendocrine neoplasia. Current concepts. Am J Clin Pathol 113: 331–335.PubMed
36.
go back to reference Capella C, Heitz PU, Hofler H, Solcia E, Kloppel G (1994) Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Digestion 55 Suppl 3: 11–23.PubMed Capella C, Heitz PU, Hofler H, Solcia E, Kloppel G (1994) Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Digestion 55 Suppl 3: 11–23.PubMed
37.
go back to reference Capella C, Heitz PU, Hofler H, Solcia E, Kloppel G (1995) Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 425: 547–560.PubMed Capella C, Heitz PU, Hofler H, Solcia E, Kloppel G (1995) Revised classification of neuroendocrine tumours of the lung, pancreas and gut. Virchows Arch 425: 547–560.PubMed
38.
go back to reference Stadler ZK, Schrader KA, Vijai J, Robson ME, Offit K (2014) Cancer Genomics and Inherited Risk. J Clin Oncol 32:687–98.PubMed Stadler ZK, Schrader KA, Vijai J, Robson ME, Offit K (2014) Cancer Genomics and Inherited Risk. J Clin Oncol 32:687–98.PubMed
39.
go back to reference Hagemann IS, Cottrell CE, Lockwood CM (2013) Design of targeted, capture-based, next generation sequencing tests for precision cancer therapy. Cancer Genet 206:420–431.PubMed Hagemann IS, Cottrell CE, Lockwood CM (2013) Design of targeted, capture-based, next generation sequencing tests for precision cancer therapy. Cancer Genet 206:420–431.PubMed
40.
41.
go back to reference Watson IR, Takahashi K, Futreal PA, Chin L (2013) Emerging patterns of somatic mutations in cancer. Nat Rev Genet 14: 703–718.PubMedCentralPubMed Watson IR, Takahashi K, Futreal PA, Chin L (2013) Emerging patterns of somatic mutations in cancer. Nat Rev Genet 14: 703–718.PubMedCentralPubMed
42.
go back to reference Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74: 5463–5467.PubMedCentralPubMed Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A 74: 5463–5467.PubMedCentralPubMed
43.
go back to reference Rossi G, Graziano P, Leone A, Migaldi M, Califano R (2013) The role of molecular analyses in the diagnosis and treatment of non-small-cell lung carcinomas. Semin Diagn Pathol 30: 298–312.PubMed Rossi G, Graziano P, Leone A, Migaldi M, Califano R (2013) The role of molecular analyses in the diagnosis and treatment of non-small-cell lung carcinomas. Semin Diagn Pathol 30: 298–312.PubMed
44.
go back to reference Chen Y, Shi JX, Pan XF, Feng J, Zhao H (2013) Identification of candidate genes for lung cancer somatic mutation test kits. Genet Mol Biol 36: 455–464.PubMedCentralPubMed Chen Y, Shi JX, Pan XF, Feng J, Zhao H (2013) Identification of candidate genes for lung cancer somatic mutation test kits. Genet Mol Biol 36: 455–464.PubMedCentralPubMed
45.
go back to reference Daniels MG, Bowman RV, Yang IA, Govindan R, Fong KM (2013) An emerging place for lung cancer genomics in 2013. J Thorac Dis 5: S491-S497.PubMedCentralPubMed Daniels MG, Bowman RV, Yang IA, Govindan R, Fong KM (2013) An emerging place for lung cancer genomics in 2013. J Thorac Dis 5: S491-S497.PubMedCentralPubMed
46.
go back to reference Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RK (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150: 1121–1134.PubMedCentralPubMed Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RK (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150: 1121–1134.PubMedCentralPubMed
47.
go back to reference Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansen S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Janne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150: 1107–1120.PubMedCentralPubMed Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, de Waal L, Sharifnia T, Brooks A, Greulich H, Banerji S, Zander T, Seidel D, Leenders F, Ansen S, Ludwig C, Engel-Riedel W, Stoelben E, Wolf J, Goparju C, Thompson K, Winckler W, Kwiatkowski D, Johnson BE, Janne PA, Miller VA, Pao W, Travis WD, Pass HI, Gabriel SB, Lander ES, Thomas RK, Garraway LA, Getz G, Meyerson M (2012) Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150: 1107–1120.PubMedCentralPubMed
48.
go back to reference Kim SC, Jung Y, Park J, Cho S, Seo C, Kim J, Kim P, Seo J, Park S, Jang I, Kim N, Yang JO, Lee B, Rho K, Keum J, Lee J, Han J, Kang S, Bae S, Choi SJ, Kim S, Lee JE, Kim W, Lee S (2013) A high-dimensional, deep-sequencing study of lung adenocarcinoma in female never-smokers. PLoS One 8: e55596.PubMedCentralPubMed Kim SC, Jung Y, Park J, Cho S, Seo C, Kim J, Kim P, Seo J, Park S, Jang I, Kim N, Yang JO, Lee B, Rho K, Keum J, Lee J, Han J, Kang S, Bae S, Choi SJ, Kim S, Lee JE, Kim W, Lee S (2013) A high-dimensional, deep-sequencing study of lung adenocarcinoma in female never-smokers. PLoS One 8: e55596.PubMedCentralPubMed
49.
go back to reference Li T, Kung HJ, Mack PC, Gandara DR (2013) Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 31: 1039–1049.PubMedCentralPubMed Li T, Kung HJ, Mack PC, Gandara DR (2013) Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 31: 1039–1049.PubMedCentralPubMed
50.
go back to reference Liu J, Lee W, Jiang Z, Chen Z, Jhunjhunwala S, Haverty PM, Gnad F, Guan Y, Gilbert HN, Stinson J, Klijn C, Guillory J, Bhatt D, Vartanian S, Walter K, Chan J, Holcomb T, Dijkgraaf P, Johnson S, Koeman J, Minna JD, Gazdar AF, Stern HM, Hoeflich KP, Wu TD, Settleman J, de Sauvage FJ, Gentleman RC, Neve RM, Stokoe D, Modrusan Z, Seshagiri S, Shames DS, Zhang Z (2012) Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Res 22: 2315–2327.PubMedCentralPubMed Liu J, Lee W, Jiang Z, Chen Z, Jhunjhunwala S, Haverty PM, Gnad F, Guan Y, Gilbert HN, Stinson J, Klijn C, Guillory J, Bhatt D, Vartanian S, Walter K, Chan J, Holcomb T, Dijkgraaf P, Johnson S, Koeman J, Minna JD, Gazdar AF, Stern HM, Hoeflich KP, Wu TD, Settleman J, de Sauvage FJ, Gentleman RC, Neve RM, Stokoe D, Modrusan Z, Seshagiri S, Shames DS, Zhang Z (2012) Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Res 22: 2315–2327.PubMedCentralPubMed
51.
go back to reference Cancer Genome Atlas Research Network (Hammerman PS, Lawrence MS, Voet D, Jing R, Cibulskis K, Sivachenko A, Stojanov P, McKenna A, Lander ES, Gabriel S, Getz G, Sougnez C, Imielinski M, Helman E, Hernandez B, Pho NH, Meyerson M, Chu A, Chun HJ, Mungall AJ, Pleasance E, Robertson A, Sipahimalani P, Stoll D, Balasundaram M, Birol I, Butterfield YS, Chuah E, Coope RJ, Corbett R, Dhalla N, Guin R, He A, Hirst C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall K, Nip KM, Olshen A, Schein JE, Slobodan JR, Tam A, Thiessen N, Varhol R, Zeng T, Zhao Y, Jones SJ, Marra MA, Saksena G, Cherniack AD, Schumacher SE, Tabak B, Carter SL, Pho NH, Nguyen H, Onofrio RC, Crenshaw A, Ardlie K, Beroukhim R, Winckler W, Hammerman PS, Getz G, Meyerson M, Protopopov A, Zhang J, Hadjipanayis A, Lee S, Xi R, Yang L, Ren X, Zhang H, Shukla S, Chen PC, Haseley P, Lee E, Chin L, Park PJ, Kucherlapati R, Socci ND, Liang Y, Schultz N, Borsu L, Lash AE, Viale A, Sander C, Ladanyi M, Auman T, Hoadley KA, Wilkerson MD, Shi Y, Liquori C, Meng S, Li L, Turman YJ, Topal MD, Tan D, Waring S, Buda E, Walsh J, Jones CD, Mieczkowski PA, Singh D, Wu J, Gulabani A, Dolina P, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Mose LE, Jefferys SR, Balu S, O’Connor BD, Prins JF, Liu J, Chiang DY, Hayes D, Perou CM, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Pan F, Van Den Berg DJ, Triche T Jr, Herman JG, Baylin SB, Laird PW, Getz G, Noble M, Voet D, Saksena G, Gehlenborg N, DiCara D, Zhang J, Zhang H, Wu CJ, Liu SY, Lawrence MS, Zou L, Sivachenko A, Lin P, Stojanov P, Jing R, Cho J, Nazaire MD, Robinson J, Thorvaldsdottir H, Mesirov J, Park PJ, Chin L, Schultz N, Sinha R, Ciriello G, Cerami E, Gross B, Jacobsen A, Gao J, Aksoy B, Weinhold N, Ramirez R, Taylor BS, Antipin Y, Reva B, Shen R, Mo Q, Seshan V, Paik PK, Ladanyi M, Sander C, Akbani R, Zhang N, Broom BM, Casasent T, Unruh A, Wakefield C, Cason R, Baggerly KA, Weinstein JN, Haussler D, Benz CC, Stuart JM, Zhu J, Szeto C, Scott GK, Yau C, Ng S, Goldstein T, Waltman P, Sokolov A, Ellrott K, Collisson EA, Zerbino D, Wilks C, Ma S, Craft B, Wilkerson MD, Auman J, Hoadley KA, Du Y, Cabanski C, Walter V, Singh D, Wu J, Gulabani A, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Mose LE, Jefferys SR, Balu S, Marron J, Liu Y, Wang K, Liu J, Prins JF, Hayes D, Perou CM, Creighton CJ, Zhang Y, Travis WD, Rekhtman N, Yi J, Aubry MC, Cheney R, Dacic S, Flieder D, Funkhouser W, Illei P, Myers J, Tsao MS, Penny R, Mallery D, Shelton T, Hatfield M, Morris S, Yena P, Shelton C, Sherman M, Paulauskis J, Meyerson M, Baylin SB, Govindan R, Akbani R, Azodo I, Beer D, Bose R, Byers LA, Carbone D, Chang LW, Chiang D, Chu A, Chun E, Collisson E, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes D, Hernandez B, Herman JG, Heymach J, Ida C, Imielinski M, Johnson B, Jurisica I, Kaufman J, Kosari F, Kucherlapati R, Kwiatkowski D, Ladanyi M, Lawrence MS, Maher CA, Mungall A, Ng S, Pao W, Peifer M, Penny R, Robertson G, Rusch V, Sander C, Schultz N, Shen R, Siegfried J, Sinha R, Sivachenko A, Sougnez C, Stoll D, Stuart J, Thomas RK, Tomaszek S, Tsao MS, Travis WD, Vaske C, Weinstein JN, Weisenberger D, Wheeler D, Wigle DA, Wilkerson MD, Wilks C, Yang P, Zhang JJ, Jensen MA, Sfeir R, Kahn AB, Chu AL, Kothiyal P, Wang Z, Snyder EE, Pontius J, Pihl TD, Ayala B, Backus M, Walton J, Baboud J, Berton DL, Nicholls MC, Srinivasan D, Raman R, Girshik S, Kigonya PA, Alonso S, Sanbhadti RN, Barletta SP, Greene JM, Pot DA, Tsao MS, Bandarchi-Chamkhaleh B, Boyd J, Weaver J, Wigle DA, Azodo IA, Tomaszek SC, Aubry MC, Ida CM, Yang P, Kosari F, Brock MV, Rodgers K, Rutledge M, Brown T, Lee B, Shin J, Trusty D, Dhir R, Siegfried JM, Potapova O, Fedosenko KV, Nemirovich-Danchenko E, Rusch V, Zakowski M, Iacocca MV, Brown J, Rabeno B, Czerwinski C, Petrelli N, Fan Z, Todaro N, Eckman J, Myers J, Rathmell W, Thorne LB, Huang M, Boice L, Hill A, Penny R, Mallery D, Curley E, Shelton C, Yena P, Morrison C, Gaudioso C, Bartlett JM, Kodeeswaran S, Zanke B, Sekhon H, David K, Juhl H, Van Le X, Kohl B, Thorp R, Nguyen VT, Nguyen VB, Sussman H, Phu BD, Hajek R, Nguyen PH, Khan KZ, Muley T, Shaw KR, Sheth M, Yang L, Buetow K, Davidsen T, Demchok JA, Eley G, Ferguson M, Dillon LA, Schaefer C, Guyer MS, Ozenberger BA, Palchik JD, Peterson J, Sofia HJ, Thomson E ) (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489: 519–525. Cancer Genome Atlas Research Network (Hammerman PS, Lawrence MS, Voet D, Jing R, Cibulskis K, Sivachenko A, Stojanov P, McKenna A, Lander ES, Gabriel S, Getz G, Sougnez C, Imielinski M, Helman E, Hernandez B, Pho NH, Meyerson M, Chu A, Chun HJ, Mungall AJ, Pleasance E, Robertson A, Sipahimalani P, Stoll D, Balasundaram M, Birol I, Butterfield YS, Chuah E, Coope RJ, Corbett R, Dhalla N, Guin R, He A, Hirst C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall K, Nip KM, Olshen A, Schein JE, Slobodan JR, Tam A, Thiessen N, Varhol R, Zeng T, Zhao Y, Jones SJ, Marra MA, Saksena G, Cherniack AD, Schumacher SE, Tabak B, Carter SL, Pho NH, Nguyen H, Onofrio RC, Crenshaw A, Ardlie K, Beroukhim R, Winckler W, Hammerman PS, Getz G, Meyerson M, Protopopov A, Zhang J, Hadjipanayis A, Lee S, Xi R, Yang L, Ren X, Zhang H, Shukla S, Chen PC, Haseley P, Lee E, Chin L, Park PJ, Kucherlapati R, Socci ND, Liang Y, Schultz N, Borsu L, Lash AE, Viale A, Sander C, Ladanyi M, Auman T, Hoadley KA, Wilkerson MD, Shi Y, Liquori C, Meng S, Li L, Turman YJ, Topal MD, Tan D, Waring S, Buda E, Walsh J, Jones CD, Mieczkowski PA, Singh D, Wu J, Gulabani A, Dolina P, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Mose LE, Jefferys SR, Balu S, O’Connor BD, Prins JF, Liu J, Chiang DY, Hayes D, Perou CM, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Pan F, Van Den Berg DJ, Triche T Jr, Herman JG, Baylin SB, Laird PW, Getz G, Noble M, Voet D, Saksena G, Gehlenborg N, DiCara D, Zhang J, Zhang H, Wu CJ, Liu SY, Lawrence MS, Zou L, Sivachenko A, Lin P, Stojanov P, Jing R, Cho J, Nazaire MD, Robinson J, Thorvaldsdottir H, Mesirov J, Park PJ, Chin L, Schultz N, Sinha R, Ciriello G, Cerami E, Gross B, Jacobsen A, Gao J, Aksoy B, Weinhold N, Ramirez R, Taylor BS, Antipin Y, Reva B, Shen R, Mo Q, Seshan V, Paik PK, Ladanyi M, Sander C, Akbani R, Zhang N, Broom BM, Casasent T, Unruh A, Wakefield C, Cason R, Baggerly KA, Weinstein JN, Haussler D, Benz CC, Stuart JM, Zhu J, Szeto C, Scott GK, Yau C, Ng S, Goldstein T, Waltman P, Sokolov A, Ellrott K, Collisson EA, Zerbino D, Wilks C, Ma S, Craft B, Wilkerson MD, Auman J, Hoadley KA, Du Y, Cabanski C, Walter V, Singh D, Wu J, Gulabani A, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Mose LE, Jefferys SR, Balu S, Marron J, Liu Y, Wang K, Liu J, Prins JF, Hayes D, Perou CM, Creighton CJ, Zhang Y, Travis WD, Rekhtman N, Yi J, Aubry MC, Cheney R, Dacic S, Flieder D, Funkhouser W, Illei P, Myers J, Tsao MS, Penny R, Mallery D, Shelton T, Hatfield M, Morris S, Yena P, Shelton C, Sherman M, Paulauskis J, Meyerson M, Baylin SB, Govindan R, Akbani R, Azodo I, Beer D, Bose R, Byers LA, Carbone D, Chang LW, Chiang D, Chu A, Chun E, Collisson E, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes D, Hernandez B, Herman JG, Heymach J, Ida C, Imielinski M, Johnson B, Jurisica I, Kaufman J, Kosari F, Kucherlapati R, Kwiatkowski D, Ladanyi M, Lawrence MS, Maher CA, Mungall A, Ng S, Pao W, Peifer M, Penny R, Robertson G, Rusch V, Sander C, Schultz N, Shen R, Siegfried J, Sinha R, Sivachenko A, Sougnez C, Stoll D, Stuart J, Thomas RK, Tomaszek S, Tsao MS, Travis WD, Vaske C, Weinstein JN, Weisenberger D, Wheeler D, Wigle DA, Wilkerson MD, Wilks C, Yang P, Zhang JJ, Jensen MA, Sfeir R, Kahn AB, Chu AL, Kothiyal P, Wang Z, Snyder EE, Pontius J, Pihl TD, Ayala B, Backus M, Walton J, Baboud J, Berton DL, Nicholls MC, Srinivasan D, Raman R, Girshik S, Kigonya PA, Alonso S, Sanbhadti RN, Barletta SP, Greene JM, Pot DA, Tsao MS, Bandarchi-Chamkhaleh B, Boyd J, Weaver J, Wigle DA, Azodo IA, Tomaszek SC, Aubry MC, Ida CM, Yang P, Kosari F, Brock MV, Rodgers K, Rutledge M, Brown T, Lee B, Shin J, Trusty D, Dhir R, Siegfried JM, Potapova O, Fedosenko KV, Nemirovich-Danchenko E, Rusch V, Zakowski M, Iacocca MV, Brown J, Rabeno B, Czerwinski C, Petrelli N, Fan Z, Todaro N, Eckman J, Myers J, Rathmell W, Thorne LB, Huang M, Boice L, Hill A, Penny R, Mallery D, Curley E, Shelton C, Yena P, Morrison C, Gaudioso C, Bartlett JM, Kodeeswaran S, Zanke B, Sekhon H, David K, Juhl H, Van Le X, Kohl B, Thorp R, Nguyen VT, Nguyen VB, Sussman H, Phu BD, Hajek R, Nguyen PH, Khan KZ, Muley T, Shaw KR, Sheth M, Yang L, Buetow K, Davidsen T, Demchok JA, Eley G, Ferguson M, Dillon LA, Schaefer C, Guyer MS, Ozenberger BA, Palchik JD, Peterson J, Sofia HJ, Thomson E ) (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489: 519–525.
52.
go back to reference Stead LF, Egan P, Devery A, Conway C, Daly C, Berri S, Wood H, Belvedere O, Papagiannopoulos K, Ryan A, Rabbitts P (2013) An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing. PLoS One 8: e78823.PubMedCentralPubMed Stead LF, Egan P, Devery A, Conway C, Daly C, Berri S, Wood H, Belvedere O, Papagiannopoulos K, Ryan A, Rabbitts P (2013) An integrated inspection of the somatic mutations in a lung squamous cell carcinoma using next-generation sequencing. PLoS One 8: e78823.PubMedCentralPubMed
53.
go back to reference Wu K, Huang RS, House L, Cho WC (2013) Next-generation sequencing for lung cancer. Future Oncol 9: 1323–1336.PubMed Wu K, Huang RS, House L, Cho WC (2013) Next-generation sequencing for lung cancer. Future Oncol 9: 1323–1336.PubMed
54.
go back to reference Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, Fulton L, Fulton RS, Zhang Q, Wendl MC, Lawrence MS, Larson DE, Chen K, Dooling DJ, Sabo A, Hawes AC, Shen H, Jhangiani SN, Lewis LR, Hall O, Zhu Y, Mathew T, Ren Y, Yao J, Scherer SE, Clerc K, Metcalf GA, Ng B, Milosavljevic A, Gonzalez-Garay ML, Osborne JR, Meyer R, Shi X, Tang Y, Koboldt DC, Lin L, Abbott R, Miner TL, Pohl C, Fewell G, Haipek C, Schmidt H, Dunford-Shore BH, Kraja A, Crosby SD, Sawyer CS, Vickery T, Sander S, Robinson J, Winckler W, Baldwin J, Chirieac LR, Dutt A, Fennell T, Hanna M, Johnson BE, Onofrio RC, Thomas RK, Tonon G, Weir BA, Zhao X, Ziaugra L, Zody MC, Giordano T, Orringer MB, Roth JA, Spitz MR, Wistuba, II, Ozenberger B, Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M, Broderick S, Yoshizawa A, Travis WD, Pao W, Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander ES, Gibbs RA, Meyerson M, Wilson RK (2008) Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455: 1069–1075.PubMedCentralPubMed Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, Fulton L, Fulton RS, Zhang Q, Wendl MC, Lawrence MS, Larson DE, Chen K, Dooling DJ, Sabo A, Hawes AC, Shen H, Jhangiani SN, Lewis LR, Hall O, Zhu Y, Mathew T, Ren Y, Yao J, Scherer SE, Clerc K, Metcalf GA, Ng B, Milosavljevic A, Gonzalez-Garay ML, Osborne JR, Meyer R, Shi X, Tang Y, Koboldt DC, Lin L, Abbott R, Miner TL, Pohl C, Fewell G, Haipek C, Schmidt H, Dunford-Shore BH, Kraja A, Crosby SD, Sawyer CS, Vickery T, Sander S, Robinson J, Winckler W, Baldwin J, Chirieac LR, Dutt A, Fennell T, Hanna M, Johnson BE, Onofrio RC, Thomas RK, Tonon G, Weir BA, Zhao X, Ziaugra L, Zody MC, Giordano T, Orringer MB, Roth JA, Spitz MR, Wistuba, II, Ozenberger B, Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M, Broderick S, Yoshizawa A, Travis WD, Pao W, Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander ES, Gibbs RA, Meyerson M, Wilson RK (2008) Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455: 1069–1075.PubMedCentralPubMed
55.
go back to reference Marchetti A, Del Grammastro M, Filice G, Felicioni L, Rossi G, Graziano P, Sartori G, Leone A, Malatesta S, Iacono M, Guetti L, Viola P, Mucilli F, Cuccurullo F, Buttitta F (2012) Complex mutations & subpopulations of deletions at exon 19 of EGFR in NSCLC revealed by next generation sequencing: potential clinical implications. PLoS One 7: e42164.PubMedCentralPubMed Marchetti A, Del Grammastro M, Filice G, Felicioni L, Rossi G, Graziano P, Sartori G, Leone A, Malatesta S, Iacono M, Guetti L, Viola P, Mucilli F, Cuccurullo F, Buttitta F (2012) Complex mutations & subpopulations of deletions at exon 19 of EGFR in NSCLC revealed by next generation sequencing: potential clinical implications. PLoS One 7: e42164.PubMedCentralPubMed
56.
go back to reference Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, Stinson J, Yue P, Zhang Y, Pant KP, Bhatt D, Ha C, Johnson S, Kennemer MI, Mohan S, Nazarenko I, Watanabe C, Sparks AB, Shames DS, Gentleman R, de Sauvage FJ, Stern H, Pandita A, Ballinger DG, Drmanac R, Modrusan Z, Seshagiri S, Zhang Z (2010) The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465: 473–477.PubMed Lee W, Jiang Z, Liu J, Haverty PM, Guan Y, Stinson J, Yue P, Zhang Y, Pant KP, Bhatt D, Ha C, Johnson S, Kennemer MI, Mohan S, Nazarenko I, Watanabe C, Sparks AB, Shames DS, Gentleman R, de Sauvage FJ, Stern H, Pandita A, Ballinger DG, Drmanac R, Modrusan Z, Seshagiri S, Zhang Z (2010) The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature 465: 473–477.PubMed
57.
go back to reference Lazar V, Suo C, Orear C, van den Oord J, Balogh Z, Guegan J, Job B, Meurice G, Ripoche H, Calza S, Hasmats J, Lundeberg J, Lacroix L, Vielh P, Dufour F, Lehtio J, Napieralski R, Eggermont A, Schmitt M, Cadranel J, Besse B, Girard P, Blackhall F, Validire P, Soria JC, Dessen P, Hansson J, Pawitan Y (2013) Integrated molecular portrait of non-small cell lung cancers. BMC Med Genomics 6: 53.PubMed Lazar V, Suo C, Orear C, van den Oord J, Balogh Z, Guegan J, Job B, Meurice G, Ripoche H, Calza S, Hasmats J, Lundeberg J, Lacroix L, Vielh P, Dufour F, Lehtio J, Napieralski R, Eggermont A, Schmitt M, Cadranel J, Besse B, Girard P, Blackhall F, Validire P, Soria JC, Dessen P, Hansson J, Pawitan Y (2013) Integrated molecular portrait of non-small cell lung cancers. BMC Med Genomics 6: 53.PubMed
58.
go back to reference Scarpa A, Sikora K, Fassan M, Rachiglio AM, Cappellesso R, Antonello D, Amato E, Mafficini A, Lambiase M, Esposito C, Bria E, Simonato F, Scardoni M, Turri G, Chilosi M, Tortora G, Fassina A, Normanno N (2013) Molecular typing of lung adenocarcinoma on cytological samples using a multigene next generation sequencing panel. PLoS One 8: e80478.PubMedCentralPubMed Scarpa A, Sikora K, Fassan M, Rachiglio AM, Cappellesso R, Antonello D, Amato E, Mafficini A, Lambiase M, Esposito C, Bria E, Simonato F, Scardoni M, Turri G, Chilosi M, Tortora G, Fassina A, Normanno N (2013) Molecular typing of lung adenocarcinoma on cytological samples using a multigene next generation sequencing panel. PLoS One 8: e80478.PubMedCentralPubMed
59.
go back to reference de Biase D, Visani M, Malapelle U, Simonato F, Cesari V, Bellevicine C, Pession A, Troncone G, Fassina A, Tallini G (2013) Next-Generation Sequencing of Lung Cancer EGFR Exons 18–21 Allows Effective Molecular Diagnosis of Small Routine Samples (Cytology and Biopsy). PLoS One 8: e83607.PubMedCentralPubMed de Biase D, Visani M, Malapelle U, Simonato F, Cesari V, Bellevicine C, Pession A, Troncone G, Fassina A, Tallini G (2013) Next-Generation Sequencing of Lung Cancer EGFR Exons 18–21 Allows Effective Molecular Diagnosis of Small Routine Samples (Cytology and Biopsy). PLoS One 8: e83607.PubMedCentralPubMed
60.
go back to reference Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 10: 472–484.PubMed Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 10: 472–484.PubMed
61.
go back to reference Moskalev EA, Stohr R, Rieker R, Hebele S, Fuchs F, Sirbu H, Mastitsky SE, Boltze C, Konig H, Agaimy A, Hartmann A, Haller F (2013) Increased detection rates of EGFR and KRAS mutations in NSCLC specimens with low tumour cell content by 454 deep sequencing. Virchows Arch 462: 409–419.PubMedCentralPubMed Moskalev EA, Stohr R, Rieker R, Hebele S, Fuchs F, Sirbu H, Mastitsky SE, Boltze C, Konig H, Agaimy A, Hartmann A, Haller F (2013) Increased detection rates of EGFR and KRAS mutations in NSCLC specimens with low tumour cell content by 454 deep sequencing. Virchows Arch 462: 409–419.PubMedCentralPubMed
62.
go back to reference Tuononen K, Maki-Nevala S, Sarhadi VK, Wirtanen A, Ronty M, Salmenkivi K, Andrews JM, Telaranta-Keerie AI, Hannula S, Lagstrom S, Ellonen P, Knuuttila A, Knuutila S (2013) Comparison of targeted next-generation sequencing (NGS) and real-time PCR in the detection of EGFR, KRAS, and BRAF mutations on formalin-fixed, paraffin-embedded tumor material of non-small cell lung carcinoma-superiority of NGS. Genes Chromosomes Cancer 52: 503–511.PubMed Tuononen K, Maki-Nevala S, Sarhadi VK, Wirtanen A, Ronty M, Salmenkivi K, Andrews JM, Telaranta-Keerie AI, Hannula S, Lagstrom S, Ellonen P, Knuuttila A, Knuutila S (2013) Comparison of targeted next-generation sequencing (NGS) and real-time PCR in the detection of EGFR, KRAS, and BRAF mutations on formalin-fixed, paraffin-embedded tumor material of non-small cell lung carcinoma-superiority of NGS. Genes Chromosomes Cancer 52: 503–511.PubMed
63.
go back to reference Luchini C, Capelli P, Fassan M, Simbolo M, Mafficini A, Pedica F, Ruzzenente A, Guglielmi A, Corbo V, Scarpa A (2014) Next-Generation Histopathologic Diagnosis: A Lesson From a Hepatic Carcinosarcoma. J Clin Oncol doi:10.1200/JCO.2012.47.5855; published online ahead of print at www.jco.org on February 3, 2014 Luchini C, Capelli P, Fassan M, Simbolo M, Mafficini A, Pedica F, Ruzzenente A, Guglielmi A, Corbo V, Scarpa A (2014) Next-Generation Histopathologic Diagnosis: A Lesson From a Hepatic Carcinosarcoma. J Clin Oncol doi:10.​1200/​JCO.​2012.​47.​5855; published online ahead of print at www.​jco.​org on February 3, 2014
64.
go back to reference Ju YS, Lee WC, Shin JY, Lee S, Bleazard T, Won JK, Kim YT, Kim JI, Kang JH, Seo JS (2012) A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 22: 436–445.PubMedCentralPubMed Ju YS, Lee WC, Shin JY, Lee S, Bleazard T, Won JK, Kim YT, Kim JI, Kang JH, Seo JS (2012) A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 22: 436–445.PubMedCentralPubMed
65.
go back to reference Majewski IJ, Mittempergher L, Davidson NM, Bosma A, Willems SM, Horlings HM, de Rink I, Greger L, Hooijer GK, Peters D, Nederlof PM, Hofland I, de Jong J, Wesseling J, Kluin RJ, Brugman W, Kerkhoven R, Nieboer F, Roepman P, Broeks A, Muley TR, Jassem J, Niklinski J, van Zandwijk N, Brazma A, Oshlack A, van den Heuvel M, Bernards R (2013) Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. J Pathol 230: 270–276.PubMed Majewski IJ, Mittempergher L, Davidson NM, Bosma A, Willems SM, Horlings HM, de Rink I, Greger L, Hooijer GK, Peters D, Nederlof PM, Hofland I, de Jong J, Wesseling J, Kluin RJ, Brugman W, Kerkhoven R, Nieboer F, Roepman P, Broeks A, Muley TR, Jassem J, Niklinski J, van Zandwijk N, Brazma A, Oshlack A, van den Heuvel M, Bernards R (2013) Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. J Pathol 230: 270–276.PubMed
66.
go back to reference Jia P, Jin H, Meador CB, Xia J, Ohashi K, Liu L, Pirazzoli V, Dahlman KB, Politi K, Michor F, Zhao Z, Pao W (2013) Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance. Genome Res 23: 1434–1445.PubMedCentralPubMed Jia P, Jin H, Meador CB, Xia J, Ohashi K, Liu L, Pirazzoli V, Dahlman KB, Politi K, Michor F, Zhao Z, Pao W (2013) Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance. Genome Res 23: 1434–1445.PubMedCentralPubMed
67.
go back to reference Huang D, Kim DW, Kotsakis A, Deng S, Lira P, Ho SN, Lee NV, Vizcarra P, Cao JQ, Christensen JG, Kim TM, Sun JM, Ahn JS, Ahn MJ, Park K, Mao M (2013) Multiplexed deep sequencing analysis of ALK kinase domain identifies resistance mutations in relapsed patients following crizotinib treatment. Genomics 102: 157–162.PubMed Huang D, Kim DW, Kotsakis A, Deng S, Lira P, Ho SN, Lee NV, Vizcarra P, Cao JQ, Christensen JG, Kim TM, Sun JM, Ahn JS, Ahn MJ, Park K, Mao M (2013) Multiplexed deep sequencing analysis of ALK kinase domain identifies resistance mutations in relapsed patients following crizotinib treatment. Genomics 102: 157–162.PubMed
68.
go back to reference Bosman F, Carneiro F, Hruban R, Theise N (2010) WHO classification of tumours of the digestive system. IARC Press, Lyon. Bosman F, Carneiro F, Hruban R, Theise N (2010) WHO classification of tumours of the digestive system. IARC Press, Lyon.
69.
go back to reference Rindi G, Falconi M, Klersy C, Albarello L, Boninsegna L, Buchler MW, Capella C, Caplin M, Couvelard A, Doglioni C, Delle Fave G, Fischer L, Fusai G, de Herder WW, Jann H, Komminoth P, de Krijger RR, La Rosa S, Luong TV, Pape U, Perren A, Ruszniewski P, Scarpa A, Schmitt A, Solcia E, Wiedenmann B (2012) TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst 104: 764–777.PubMed Rindi G, Falconi M, Klersy C, Albarello L, Boninsegna L, Buchler MW, Capella C, Caplin M, Couvelard A, Doglioni C, Delle Fave G, Fischer L, Fusai G, de Herder WW, Jann H, Komminoth P, de Krijger RR, La Rosa S, Luong TV, Pape U, Perren A, Ruszniewski P, Scarpa A, Schmitt A, Solcia E, Wiedenmann B (2012) TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst 104: 764–777.PubMed
70.
go back to reference Yang Z, Tang LH, Klimstra DS (2013) Gastroenteropancreatic neuroendocrine neoplasms: historical context and current issues. Semin Diagn Pathol 30: 186–196.PubMed Yang Z, Tang LH, Klimstra DS (2013) Gastroenteropancreatic neuroendocrine neoplasms: historical context and current issues. Semin Diagn Pathol 30: 186–196.PubMed
71.
go back to reference Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S (2010) The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 39: 707–712.PubMed Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S (2010) The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 39: 707–712.PubMed
72.
go back to reference Travis W, Colby T, Corrin B, Shimosato Y, Brambilla E (1999) Histological typing of lung and pleural tumours. Springer Verlag, Berlin Heidelberg New York. Travis W, Colby T, Corrin B, Shimosato Y, Brambilla E (1999) Histological typing of lung and pleural tumours. Springer Verlag, Berlin Heidelberg New York.
73.
go back to reference Jones MH, Virtanen C, Honjoh D, Miyoshi T, Satoh Y, Okumura S, Nakagawa K, Nomura H, Ishikawa Y (2004) Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles. Lancet 363: 775–781.PubMed Jones MH, Virtanen C, Honjoh D, Miyoshi T, Satoh Y, Okumura S, Nakagawa K, Nomura H, Ishikawa Y (2004) Two prognostically significant subtypes of high-grade lung neuroendocrine tumours independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles. Lancet 363: 775–781.PubMed
74.
go back to reference Nicholson SA, Beasley MB, Brambilla E, Hasleton PS, Colby TV, Sheppard MN, Falk R, Travis WD (2002) Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol 26: 1184–1197.PubMed Nicholson SA, Beasley MB, Brambilla E, Hasleton PS, Colby TV, Sheppard MN, Falk R, Travis WD (2002) Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol 26: 1184–1197.PubMed
75.
go back to reference Tsuchiya R, Suzuki K, Ichinose Y, Watanabe Y, Yasumitsu T, Ishizuka N, Kato H (2005) Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with completely resected stage I-IIIa small cell lung cancer: the Japan Clinical Oncology Lung Cancer Study Group Trial (JCOG9101). J Thorac Cardiovasc Surg 129: 977–983.PubMed Tsuchiya R, Suzuki K, Ichinose Y, Watanabe Y, Yasumitsu T, Ishizuka N, Kato H (2005) Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with completely resected stage I-IIIa small cell lung cancer: the Japan Clinical Oncology Lung Cancer Study Group Trial (JCOG9101). J Thorac Cardiovasc Surg 129: 977–983.PubMed
76.
go back to reference Brock MV, Hooker CM, Syphard JE, Westra W, Xu L, Alberg AJ, Mason D, Baylin SB, Herman JG, Yung RC, Brahmer J, Rudin CM, Ettinger DS, Yang SC (2005) Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: Its time has come. J Thorac Cardiovasc Surg 129: 64–72.PubMed Brock MV, Hooker CM, Syphard JE, Westra W, Xu L, Alberg AJ, Mason D, Baylin SB, Herman JG, Yung RC, Brahmer J, Rudin CM, Ettinger DS, Yang SC (2005) Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: Its time has come. J Thorac Cardiovasc Surg 129: 64–72.PubMed
77.
go back to reference Rea F, Callegaro D, Favaretto A, Loy M, Paccagnella A, Fantoni U, Festi G, Sartori F (1998) Long term results of surgery and chemotherapy in small cell lung cancer. Eur J Cardiothorac Surg 14: 398–402.PubMed Rea F, Callegaro D, Favaretto A, Loy M, Paccagnella A, Fantoni U, Festi G, Sartori F (1998) Long term results of surgery and chemotherapy in small cell lung cancer. Eur J Cardiothorac Surg 14: 398–402.PubMed
78.
go back to reference Bastrurk O, Yang Z, Tang L, Hruban R, McCall C, Adsay V, Krasinkas A, Jang K-T, Bellizzi A, Shi C, Klimstra D (2013) Increased (>20%) Ki-67 proliferation index in morphologically well differentiated pancreatic neuroendocrine tumors (PanNETs) correlates with decreased overall survival (abstract #1761). Mod Pathol 26: 423A. Bastrurk O, Yang Z, Tang L, Hruban R, McCall C, Adsay V, Krasinkas A, Jang K-T, Bellizzi A, Shi C, Klimstra D (2013) Increased (>20%) Ki-67 proliferation index in morphologically well differentiated pancreatic neuroendocrine tumors (PanNETs) correlates with decreased overall survival (abstract #1761). Mod Pathol 26: 423A.
79.
go back to reference Basturk O, Tang L, Hruban RH, Adsay V, Yang Z, Krasinskas AM, Vakiani E, La Rosa S, Jang KT, Frankel WL, Liu X, Zhang L, Giordano TJ, Bellizzi AM, Chen JH, Shi C, Allen P, Reidy DL, Wolfgang CL, Saka B, Rezaee N, Deshpande V, Klimstra DS (2014) Poorly Differentiated Neuroendocrine Carcinomas of the Pancreas: A Clinicopathologic Analysis of 44 Cases. Am J Surg Pathol 38:437–447.PubMed Basturk O, Tang L, Hruban RH, Adsay V, Yang Z, Krasinskas AM, Vakiani E, La Rosa S, Jang KT, Frankel WL, Liu X, Zhang L, Giordano TJ, Bellizzi AM, Chen JH, Shi C, Allen P, Reidy DL, Wolfgang CL, Saka B, Rezaee N, Deshpande V, Klimstra DS (2014) Poorly Differentiated Neuroendocrine Carcinomas of the Pancreas: A Clinicopathologic Analysis of 44 Cases. Am J Surg Pathol 38:437–447.PubMed
80.
go back to reference Oberg K, Knigge U, Kwekkeboom D, Perren A (2012) Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23 Suppl 7: vii124-130.PubMed Oberg K, Knigge U, Kwekkeboom D, Perren A (2012) Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23 Suppl 7: vii124-130.PubMed
81.
go back to reference Tsutsumi K, Ohtsuka T, Fujino M, Nakashima H, Aishima S, Ueda J, Takahata S, Nakamura M, Oda Y, Tanaka M (2013) Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification. J Hepatobiliary Pancreat Sci Oct 20. doi:10.1002/jhbp.47. [Epub ahead of print] Tsutsumi K, Ohtsuka T, Fujino M, Nakashima H, Aishima S, Ueda J, Takahata S, Nakamura M, Oda Y, Tanaka M (2013) Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification. J Hepatobiliary Pancreat Sci Oct 20. doi:10.​1002/​jhbp.​47. [Epub ahead of print]
82.
go back to reference Welin S, Sorbye H, Sebjornsen S, Knappskog S, Busch C, Oberg K (2011) Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer 117: 4617–4622.PubMed Welin S, Sorbye H, Sebjornsen S, Knappskog S, Busch C, Oberg K (2011) Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer 117: 4617–4622.PubMed
83.
go back to reference Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gonen M, Jensen RT, Kidd M, Kulke MH, Lloyd RV, Moran C, Moss SF, Oberg K, O’Toole D, Rindi G, Robert ME, Suster S, Tang LH, Tzen CY, Washington MK, Wiedenmann B, Yao J (2010) Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol 34: 300–313.PubMed Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gonen M, Jensen RT, Kidd M, Kulke MH, Lloyd RV, Moran C, Moss SF, Oberg K, O’Toole D, Rindi G, Robert ME, Suster S, Tang LH, Tzen CY, Washington MK, Wiedenmann B, Yao J (2010) Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol 34: 300–313.PubMed
84.
go back to reference Moran CA, Suster S (2007) Neuroendocrine carcinomas (carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma): current concepts. Hematol Oncol Clin North Am 21: 395–407; vii.PubMed Moran CA, Suster S (2007) Neuroendocrine carcinomas (carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma): current concepts. Hematol Oncol Clin North Am 21: 395–407; vii.PubMed
85.
go back to reference Pelosi G, Rindi G, Travis WD, Papotti M (2014) Ki-67 antigen in lung neuroendocrine tumors: unraveling a role in clinical practice. J Thorac Oncol 9: 273–284.PubMed Pelosi G, Rindi G, Travis WD, Papotti M (2014) Ki-67 antigen in lung neuroendocrine tumors: unraveling a role in clinical practice. J Thorac Oncol 9: 273–284.PubMed
86.
go back to reference Pelosi G, Bresaola E, Bogina G, Pasini F, Rodella S, Castelli P, Iacono C, Serio G, Zamboni G (1996) Endocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy: a comparative study with proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variables. Hum Pathol 27: 1124–1134.PubMed Pelosi G, Bresaola E, Bogina G, Pasini F, Rodella S, Castelli P, Iacono C, Serio G, Zamboni G (1996) Endocrine tumors of the pancreas: Ki-67 immunoreactivity on paraffin sections is an independent predictor for malignancy: a comparative study with proliferating-cell nuclear antigen and progesterone receptor protein immunostaining, mitotic index, and other clinicopathologic variables. Hum Pathol 27: 1124–1134.PubMed
87.
go back to reference Pelosi G, Zamboni G (1996) Proliferation Markers and Their Uses in the Study of Endocrine Tumors. Endocr Pathol 7: 103–119.PubMed Pelosi G, Zamboni G (1996) Proliferation Markers and Their Uses in the Study of Endocrine Tumors. Endocr Pathol 7: 103–119.PubMed
88.
go back to reference Pelosi G, Zamboni G, Doglioni C, Rodella S, Bresaola E, Iacono C, Serio G, Iannucci A, Scarpa A (1992) Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas. Am J Surg Pathol 16: 1215–1225.PubMed Pelosi G, Zamboni G, Doglioni C, Rodella S, Bresaola E, Iacono C, Serio G, Iannucci A, Scarpa A (1992) Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas. Am J Surg Pathol 16: 1215–1225.PubMed
89.
go back to reference Morin E, Cheng S, Mete O, Serra S, Araujo PB, Temple S, Cleary S, Gallinger S, Greig PD, McGilvray I, Wei A, Asa SL, Ezzat S (2013) Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior. Cancer Med 2: 701–711.PubMedCentralPubMed Morin E, Cheng S, Mete O, Serra S, Araujo PB, Temple S, Cleary S, Gallinger S, Greig PD, McGilvray I, Wei A, Asa SL, Ezzat S (2013) Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior. Cancer Med 2: 701–711.PubMedCentralPubMed
90.
go back to reference Fernandez-Figueras MT, Puig L, Musulen E, Gilaberte M, Ferrandiz C, Lerma E, Ariza A (2005) Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma. Histopathology 46: 614–621.PubMed Fernandez-Figueras MT, Puig L, Musulen E, Gilaberte M, Ferrandiz C, Lerma E, Ariza A (2005) Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma. Histopathology 46: 614–621.PubMed
91.
go back to reference Han B, Sun JM, Ahn JS, Park K, Ahn MJ (2013) Clinical outcomes of atypical carcinoid tumors of the lung and thymus: 7-year experience of a rare malignancy at single institute. Med Oncol 30: 479.PubMed Han B, Sun JM, Ahn JS, Park K, Ahn MJ (2013) Clinical outcomes of atypical carcinoid tumors of the lung and thymus: 7-year experience of a rare malignancy at single institute. Med Oncol 30: 479.PubMed
92.
go back to reference Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Korner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449: 395–401.PubMedCentralPubMed Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Korner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 449: 395–401.PubMedCentralPubMed
93.
go back to reference Zahel T, Krysa S, Herpel E, Stenzinger A, Goeppert B, Schirmacher P, Hoffmann H, Schnabel PA, Warth A (2012) Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach. Virchows Arch 460: 299–308.PubMed Zahel T, Krysa S, Herpel E, Stenzinger A, Goeppert B, Schirmacher P, Hoffmann H, Schnabel PA, Warth A (2012) Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach. Virchows Arch 460: 299–308.PubMed
94.
go back to reference Grimaldi F, Muser D, Beltrami CA, Machin P, Morelli A, Pizzolitto S, Talmassons G, Marciello F, Colao AA, Monaco R, Monaco G, Faggiano A (2011) Partitioning of bronchopulmonary carcinoids in two different prognostic categories by ki-67 score. Front Endocrinol (Lausanne) Vol. 2, Article 20, Pages 1–6 Grimaldi F, Muser D, Beltrami CA, Machin P, Morelli A, Pizzolitto S, Talmassons G, Marciello F, Colao AA, Monaco R, Monaco G, Faggiano A (2011) Partitioning of bronchopulmonary carcinoids in two different prognostic categories by ki-67 score. Front Endocrinol (Lausanne) Vol. 2, Article 20, Pages 1–6
95.
go back to reference Costes V, Marty-Ane C, Picot MC, Serre I, Pujol JL, Mary H, Baldet P (1995) Typical and atypical bronchopulmonary carcinoid tumors: a clinicopathologic and KI-67-labeling study. Hum Pathol 26: 740–745.PubMed Costes V, Marty-Ane C, Picot MC, Serre I, Pujol JL, Mary H, Baldet P (1995) Typical and atypical bronchopulmonary carcinoid tumors: a clinicopathologic and KI-67-labeling study. Hum Pathol 26: 740–745.PubMed
96.
go back to reference Rugge M, Fassan M, Clemente R, Rizzardi G, Giacomelli L, Pennelli G, Mescoli C, Segat D, Rea F (2008) Bronchopulmonary carcinoid: phenotype and long-term outcome in a single-institution series of Italian patients. Clin Cancer Res 14: 149–154.PubMed Rugge M, Fassan M, Clemente R, Rizzardi G, Giacomelli L, Pennelli G, Mescoli C, Segat D, Rea F (2008) Bronchopulmonary carcinoid: phenotype and long-term outcome in a single-institution series of Italian patients. Clin Cancer Res 14: 149–154.PubMed
97.
go back to reference Walts AE, Ines D, Marchevsky AM (2012) Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumors. Mod Pathol 25: 1258–1264.PubMed Walts AE, Ines D, Marchevsky AM (2012) Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumors. Mod Pathol 25: 1258–1264.PubMed
98.
go back to reference Granberg D, Wilander E, Oberg K, Skogseid B (2000) Prognostic markers in patients with typical bronchial carcinoid tumors. J Clin Endocrinol Metab 85: 3425–3430.PubMed Granberg D, Wilander E, Oberg K, Skogseid B (2000) Prognostic markers in patients with typical bronchial carcinoid tumors. J Clin Endocrinol Metab 85: 3425–3430.PubMed
99.
go back to reference Helpap B, Kollermann J (2001) Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs. Are there indications for a neuroendocrine tumor-carcinoma sequence? Virchows Arch 438: 86–91.PubMed Helpap B, Kollermann J (2001) Immunohistochemical analysis of the proliferative activity of neuroendocrine tumors from various organs. Are there indications for a neuroendocrine tumor-carcinoma sequence? Virchows Arch 438: 86–91.PubMed
100.
go back to reference Igarashi T, Jiang SX, Kameya T, Asamura H, Sato Y, Nagai K, Okayasu I (2004) Divergent cyclin B1 expression and Rb/p16/cyclin D1 pathway aberrations among pulmonary neuroendocrine tumors. Mod Pathol 17: 1259–1267.PubMed Igarashi T, Jiang SX, Kameya T, Asamura H, Sato Y, Nagai K, Okayasu I (2004) Divergent cyclin B1 expression and Rb/p16/cyclin D1 pathway aberrations among pulmonary neuroendocrine tumors. Mod Pathol 17: 1259–1267.PubMed
101.
go back to reference Laitinen KL, Soini Y, Mattila J, Paakko P (2000) Atypical bronchopulmonary carcinoids show a tendency toward increased apoptotic and proliferative activity. Cancer 88: 1590–1598.PubMed Laitinen KL, Soini Y, Mattila J, Paakko P (2000) Atypical bronchopulmonary carcinoids show a tendency toward increased apoptotic and proliferative activity. Cancer 88: 1590–1598.PubMed
102.
go back to reference Pelosi G, Rodriguez J, Viale G, Rosai J (2005) Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: a major pitfall in the management of lung cancer patients. Am J Surg Pathol 29: 179–187.PubMed Pelosi G, Rodriguez J, Viale G, Rosai J (2005) Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: a major pitfall in the management of lung cancer patients. Am J Surg Pathol 29: 179–187.PubMed
103.
go back to reference Skov BG, Holm B, Erreboe A, Skov T, Mellemgaard A (2010) ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: distribution and impact on survival. J Thorac Oncol 5: 453–459.PubMed Skov BG, Holm B, Erreboe A, Skov T, Mellemgaard A (2010) ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: distribution and impact on survival. J Thorac Oncol 5: 453–459.PubMed
104.
go back to reference Warth A, Fink L, Fisseler-Eckhoff A, Jonigk D, Keller M, Ott G, Rieker RJ, Sinn P, Soder S, Soltermann A, Willenbrock K, Weichert W (2013) Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids. Virchows Arch 462: 507–513.PubMed Warth A, Fink L, Fisseler-Eckhoff A, Jonigk D, Keller M, Ott G, Rieker RJ, Sinn P, Soder S, Soltermann A, Willenbrock K, Weichert W (2013) Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids. Virchows Arch 462: 507–513.PubMed
105.
go back to reference McCall CM, Shi C, Cornish TC, Klimstra DS, Tang LH, Basturk O, Mun LJ, Ellison TA, Wolfgang CL, Choti MA, Schulick RD, Edil BH, Hruban RH (2013) Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol 37: 1671–1677.PubMed McCall CM, Shi C, Cornish TC, Klimstra DS, Tang LH, Basturk O, Mun LJ, Ellison TA, Wolfgang CL, Choti MA, Schulick RD, Edil BH, Hruban RH (2013) Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate. Am J Surg Pathol 37: 1671–1677.PubMed
106.
go back to reference Clinical Lung Cancer Genome Project (CLCGP); Network Genomic Medicine (NGM) (Seidel D, Zander T, Heukamp LC, Peifer M, Bos M, Fernández-Cuesta L, Leenders F, Lu X, Ansén S, Gardizi M, Nguyen C, Berg J, Russell P, Wainer Z, Schildhaus HU, Rogers TM, Solomon B, Pao W, Carter SL, Getz G, Hayes D, Wilkerson MD, Thunnissen E, Travis WD, Perner S, Wright G, Brambilla E, Büttner R, Wolf J, Thomas RK, Gabler F, Wilkening I, Müller C, Dahmen I, Menon R, König K, Albus K, Merkelbach-Bruse S, Fassunke J, Schmitz K, Kuenstlinger H, Kleine MA, Binot E, Querings S, Altmüller J, Bäßmann I, Nürnberg P, Schneider PM, Bogus M, Büttner R, Perner S, Russell P, Thunnissen E, Travis WD, Brambilla E, Soltermann A, Moch H, Brustugun OT, Solberg S, Lund-Iversen M, Helland Å, Muley T, Hoffmann H, Schnabel PA, Chen Y, Groen H, Timens W, Sietsma H, Clement JH, Weder W, Sänger J, Stoelben E, Ludwig C, Engel-Riedel W, Smit E, Heideman DA, Snijders PJ, Nogova L, Sos ML, Mattonet C, Töpelt K, Scheffler M, Goekkurt E, Kappes R, Krüger S, Kambartel K, Behringer D, Schulte W, Galetke W, Randerath W, Heldwein M, Schlesinger A, Serke M, Hekmat K, Frank KF, Schnell R, Reiser M, Hünerlitürkoglu AN, Schmitz S, Meffert L, Ko YD, Litt-Lampe M, Gerigk U, Fricke R, Besse B, Brambilla C, Lantuejoul S, Lorimier P, Moro-Sibilot D, Cappuzzo F, Ligorio C, Damiani S, Field JK, Hyde R, Validire P, Girard P, Muscarella LA, Fazio VM, Hallek M, Soria JC, Carter SL, Getz G, Hayes D, Wilkerson MD, Achter V, Lang U, Seidel D, Zander T, Heukamp LC, Peifer M, Bos M, Pao W, Travis WD, Brambilla E, Büttner R, Wolf J, Thomas RK, Büttner R, Wolf J, Thomas RK) (2013). A genomics-based classification of human lung tumors. Sci Transl Med 5: 209ra153. Clinical Lung Cancer Genome Project (CLCGP); Network Genomic Medicine (NGM) (Seidel D, Zander T, Heukamp LC, Peifer M, Bos M, Fernández-Cuesta L, Leenders F, Lu X, Ansén S, Gardizi M, Nguyen C, Berg J, Russell P, Wainer Z, Schildhaus HU, Rogers TM, Solomon B, Pao W, Carter SL, Getz G, Hayes D, Wilkerson MD, Thunnissen E, Travis WD, Perner S, Wright G, Brambilla E, Büttner R, Wolf J, Thomas RK, Gabler F, Wilkening I, Müller C, Dahmen I, Menon R, König K, Albus K, Merkelbach-Bruse S, Fassunke J, Schmitz K, Kuenstlinger H, Kleine MA, Binot E, Querings S, Altmüller J, Bäßmann I, Nürnberg P, Schneider PM, Bogus M, Büttner R, Perner S, Russell P, Thunnissen E, Travis WD, Brambilla E, Soltermann A, Moch H, Brustugun OT, Solberg S, Lund-Iversen M, Helland Å, Muley T, Hoffmann H, Schnabel PA, Chen Y, Groen H, Timens W, Sietsma H, Clement JH, Weder W, Sänger J, Stoelben E, Ludwig C, Engel-Riedel W, Smit E, Heideman DA, Snijders PJ, Nogova L, Sos ML, Mattonet C, Töpelt K, Scheffler M, Goekkurt E, Kappes R, Krüger S, Kambartel K, Behringer D, Schulte W, Galetke W, Randerath W, Heldwein M, Schlesinger A, Serke M, Hekmat K, Frank KF, Schnell R, Reiser M, Hünerlitürkoglu AN, Schmitz S, Meffert L, Ko YD, Litt-Lampe M, Gerigk U, Fricke R, Besse B, Brambilla C, Lantuejoul S, Lorimier P, Moro-Sibilot D, Cappuzzo F, Ligorio C, Damiani S, Field JK, Hyde R, Validire P, Girard P, Muscarella LA, Fazio VM, Hallek M, Soria JC, Carter SL, Getz G, Hayes D, Wilkerson MD, Achter V, Lang U, Seidel D, Zander T, Heukamp LC, Peifer M, Bos M, Pao W, Travis WD, Brambilla E, Büttner R, Wolf J, Thomas RK, Büttner R, Wolf J, Thomas RK) (2013). A genomics-based classification of human lung tumors. Sci Transl Med 5: 209ra153.
107.
go back to reference Fernandez-Cuesta L, Peifer M, Lu X, Sun R, Ozretić L, Seidel D, Zander T, Leenders F, George J, Müller C, Dahmen I, Pinther B, Bosco G, Konrad K, Altmüller J, Nürnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soltermann A, Brustugun OT, Helland A, Solberg S, Lund-Iversen M, Ansén S, Stoelben E, Wright GM, Russell P, Wainer Z, Solomon B, Field JK, Hyde R, Davies MP, Heukamp LC, Petersen I, Perner S, Lovly CM, Cappuzzo F, Travis WD, Wolf J, Vingron M, Brambilla E, Haas SA, Buettner R, Thomas RK (2014) Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nat Commun 5:3518. doi:10.1038/ncomms4518.PubMed Fernandez-Cuesta L, Peifer M, Lu X, Sun R, Ozretić L, Seidel D, Zander T, Leenders F, George J, Müller C, Dahmen I, Pinther B, Bosco G, Konrad K, Altmüller J, Nürnberg P, Achter V, Lang U, Schneider PM, Bogus M, Soltermann A, Brustugun OT, Helland A, Solberg S, Lund-Iversen M, Ansén S, Stoelben E, Wright GM, Russell P, Wainer Z, Solomon B, Field JK, Hyde R, Davies MP, Heukamp LC, Petersen I, Perner S, Lovly CM, Cappuzzo F, Travis WD, Wolf J, Vingron M, Brambilla E, Haas SA, Buettner R, Thomas RK (2014) Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nat Commun 5:3518. doi:10.​1038/​ncomms4518.PubMed
108.
go back to reference Iwakawa R, Takenaka M, Kohno T, Shimada Y, Totoki Y, Shibata T, Tsuta K, Nishikawa R, Noguchi M, Sato-Otsubo A, Ogawa S, Yokota J (2013) Genome-wide identification of genes with amplification and/or fusion in small cell lung cancer. Genes Chromosomes Cancer 52: 802–816.PubMedCentralPubMed Iwakawa R, Takenaka M, Kohno T, Shimada Y, Totoki Y, Shibata T, Tsuta K, Nishikawa R, Noguchi M, Sato-Otsubo A, Ogawa S, Yokota J (2013) Genome-wide identification of genes with amplification and/or fusion in small cell lung cancer. Genes Chromosomes Cancer 52: 802–816.PubMedCentralPubMed
109.
go back to reference Peifer M, Fernandez-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Muller C, Di Cerbo V, Schildhaus HU, Altmuller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Bohm D, Ansen S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grutter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sanger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Buttner R, Wolf J, Nurnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, Thomas RK (2012) Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 44: 1104–1110.PubMed Peifer M, Fernandez-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Muller C, Di Cerbo V, Schildhaus HU, Altmuller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Bohm D, Ansen S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grutter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sanger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Buttner R, Wolf J, Nurnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, Thomas RK (2012) Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 44: 1104–1110.PubMed
110.
go back to reference Rudin CM, Durinck S, Stawiski EW, Poirier JT, Modrusan Z, Shames DS, Bergbower EA, Guan Y, Shin J, Guillory J, Rivers CS, Foo CK, Bhatt D, Stinson J, Gnad F, Haverty PM, Gentleman R, Chaudhuri S, Janakiraman V, Jaiswal BS, Parikh C, Yuan W, Zhang Z, Koeppen H, Wu TD, Stern HM, Yauch RL, Huffman KE, Paskulin DD, Illei PB, Varella-Garcia M, Gazdar AF, de Sauvage FJ, Bourgon R, Minna JD, Brock MV, Seshagiri S (2012) Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet 44: 1111–1116.PubMedCentralPubMed Rudin CM, Durinck S, Stawiski EW, Poirier JT, Modrusan Z, Shames DS, Bergbower EA, Guan Y, Shin J, Guillory J, Rivers CS, Foo CK, Bhatt D, Stinson J, Gnad F, Haverty PM, Gentleman R, Chaudhuri S, Janakiraman V, Jaiswal BS, Parikh C, Yuan W, Zhang Z, Koeppen H, Wu TD, Stern HM, Yauch RL, Huffman KE, Paskulin DD, Illei PB, Varella-Garcia M, Gazdar AF, de Sauvage FJ, Bourgon R, Minna JD, Brock MV, Seshagiri S (2012) Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet 44: 1111–1116.PubMedCentralPubMed
111.
go back to reference Karpathakis A, Dibra H, Thirlwell C (2013) Neuroendocrine tumours: cracking the epigenetic code. Endocr Relat Cancer 20: R65-82.PubMed Karpathakis A, Dibra H, Thirlwell C (2013) Neuroendocrine tumours: cracking the epigenetic code. Endocr Relat Cancer 20: R65-82.PubMed
113.
go back to reference Swarts DR, Ramaekers FC, Speel EJ (2012) Molecular and cellular biology of neuroendocrine lung tumors: Evidence for separate biological entities. Biochim Biophys Acta 1826: 255–271.PubMed Swarts DR, Ramaekers FC, Speel EJ (2012) Molecular and cellular biology of neuroendocrine lung tumors: Evidence for separate biological entities. Biochim Biophys Acta 1826: 255–271.PubMed
114.
go back to reference Cakir M, Grossman A (2011) The molecular pathogenesis and management of bronchial carcinoids. Expert Opin Ther Targets 15: 457–491.PubMed Cakir M, Grossman A (2011) The molecular pathogenesis and management of bronchial carcinoids. Expert Opin Ther Targets 15: 457–491.PubMed
115.
go back to reference Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M (2011) Tumour evolution inferred by single-cell sequencing. Nature 472: 90–94.PubMed Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M (2011) Tumour evolution inferred by single-cell sequencing. Nature 472: 90–94.PubMed
116.
go back to reference Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD, McMichael JF, Wallis JW, Lu C, Shen D, Harris CC, Dooling DJ, Fulton RS, Fulton LL, Chen K, Schmidt H, Kalicki-Veizer J, Magrini VJ, Cook L, McGrath SD, Vickery TL, Wendl MC, Heath S, Watson MA, Link DC, Tomasson MH, Shannon WD, Payton JE, Kulkarni S, Westervelt P, Walter MJ, Graubert TA, Mardis ER, Wilson RK, DiPersio JF (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481: 506–510.PubMedCentralPubMed Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD, McMichael JF, Wallis JW, Lu C, Shen D, Harris CC, Dooling DJ, Fulton RS, Fulton LL, Chen K, Schmidt H, Kalicki-Veizer J, Magrini VJ, Cook L, McGrath SD, Vickery TL, Wendl MC, Heath S, Watson MA, Link DC, Tomasson MH, Shannon WD, Payton JE, Kulkarni S, Westervelt P, Walter MJ, Graubert TA, Mardis ER, Wilson RK, DiPersio JF (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481: 506–510.PubMedCentralPubMed
117.
go back to reference Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883–892.PubMed Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366: 883–892.PubMed
118.
go back to reference Proskuryakov SY, Gabai VL (2010) Mechanisms of tumor cell necrosis. Curr Pharm Des 16: 56–68.PubMed Proskuryakov SY, Gabai VL (2010) Mechanisms of tumor cell necrosis. Curr Pharm Des 16: 56–68.PubMed
119.
go back to reference Francis JM, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR, Banck MS, Kanwar R, Kulkarni AA, Karpathakis A, Manzo V, Contractor T, Philips J, Nickerson E, Pho N, Hooshmand SM, Brais LK, Lawrence MS, Pugh T, McKenna A, Sivachenko A, Cibulskis K, Carter SL, Ojesina AI, Freeman S, Jones RT, Voet D, Saksena G, Auclair D, Onofrio R, Shefler E, Sougnez C, Grimsby J, Green L, Lennon N, Meyer T, Caplin M, Chung DC, Beutler AS, Ogino S, Thirlwell C, Shivdasani R, Asa SL, Harris CR, Getz G, Kulke M, Meyerson M (2013) Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet 45: 1483–1486.PubMed Francis JM, Kiezun A, Ramos AH, Serra S, Pedamallu CS, Qian ZR, Banck MS, Kanwar R, Kulkarni AA, Karpathakis A, Manzo V, Contractor T, Philips J, Nickerson E, Pho N, Hooshmand SM, Brais LK, Lawrence MS, Pugh T, McKenna A, Sivachenko A, Cibulskis K, Carter SL, Ojesina AI, Freeman S, Jones RT, Voet D, Saksena G, Auclair D, Onofrio R, Shefler E, Sougnez C, Grimsby J, Green L, Lennon N, Meyer T, Caplin M, Chung DC, Beutler AS, Ogino S, Thirlwell C, Shivdasani R, Asa SL, Harris CR, Getz G, Kulke M, Meyerson M (2013) Somatic mutation of CDKN1B in small intestine neuroendocrine tumors. Nat Genet 45: 1483–1486.PubMed
120.
go back to reference Papadopoulos A, Guida F, Leffondre K, Cenee S, Cyr D, Schmaus A, Radoi L, Paget-Bailly S, Carton M, Menvielle G, Woronoff AS, Tretarre B, Luce D, Stucker I (2014) Heavy smoking and lung cancer: Are women at higher risk? Result of the ICARE study. Br J Cancer 110: 1385–1391.PubMed Papadopoulos A, Guida F, Leffondre K, Cenee S, Cyr D, Schmaus A, Radoi L, Paget-Bailly S, Carton M, Menvielle G, Woronoff AS, Tretarre B, Luce D, Stucker I (2014) Heavy smoking and lung cancer: Are women at higher risk? Result of the ICARE study. Br J Cancer 110: 1385–1391.PubMed
121.
go back to reference Beasley MB, Lantuejoul S, Abbondanzo S, Chu WS, Hasleton PS, Travis WD, Brambilla E (2003) The P16/cyclin D1/Rb pathway in neuroendocrine tumors of the lung. Hum Pathol 34: 136–142.PubMed Beasley MB, Lantuejoul S, Abbondanzo S, Chu WS, Hasleton PS, Travis WD, Brambilla E (2003) The P16/cyclin D1/Rb pathway in neuroendocrine tumors of the lung. Hum Pathol 34: 136–142.PubMed
122.
go back to reference Swarts DR, Claessen SM, Jonkers YM, van Suylen RJ, Dingemans AM, de Herder WW, de Krijger RR, Smit EF, Thunnissen FB, Seldenrijk CA, Vink A, Perren A, Ramaekers FC, Speel EJ (2011) Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome. Am J Pathol 179: 1129–1137.PubMedCentralPubMed Swarts DR, Claessen SM, Jonkers YM, van Suylen RJ, Dingemans AM, de Herder WW, de Krijger RR, Smit EF, Thunnissen FB, Seldenrijk CA, Vink A, Perren A, Ramaekers FC, Speel EJ (2011) Deletions of 11q22.3-q25 are associated with atypical lung carcinoids and poor clinical outcome. Am J Pathol 179: 1129–1137.PubMedCentralPubMed
123.
go back to reference Swarts DR, Scarpa A, Corbo V, Van Criekinge W, van Engeland M, Gatti G, Henfling ME, Papotti M, Perren A, Ramaekers FC, Speel EJ, Volante M (2014) MEN1 Gene Mutation and Reduced Expression Are Associated With Poor Prognosis in Pulmonary Carcinoids. J Clin Endocrinol Metab 99: E374-378.PubMed Swarts DR, Scarpa A, Corbo V, Van Criekinge W, van Engeland M, Gatti G, Henfling ME, Papotti M, Perren A, Ramaekers FC, Speel EJ, Volante M (2014) MEN1 Gene Mutation and Reduced Expression Are Associated With Poor Prognosis in Pulmonary Carcinoids. J Clin Endocrinol Metab 99: E374-378.PubMed
124.
go back to reference Marchetti A, Felicioni L, Pelosi G, Del Grammastro M, Fumagalli C, Sciarrotta M, Malatesta S, Chella A, Barassi F, Mucilli F, Camplese P, D’Antuono T, Sacco R, Buttitta F (2008) Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung. Hum Mutat 29: 609–616.PubMed Marchetti A, Felicioni L, Pelosi G, Del Grammastro M, Fumagalli C, Sciarrotta M, Malatesta S, Chella A, Barassi F, Mucilli F, Camplese P, D’Antuono T, Sacco R, Buttitta F (2008) Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung. Hum Mutat 29: 609–616.PubMed
125.
go back to reference Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3: 75ra26.PubMedCentralPubMed Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3: 75ra26.PubMedCentralPubMed
126.
go back to reference Brambilla E, Moro D, Gazzeri S, Brichon PY, Nagy-Mignotte H, Morel F, Jacrot M, Brambilla C (1991) Cytotoxic chemotherapy induces cell differentiation in small-cell lung carcinoma. J Clin Oncol 9: 50–61.PubMed Brambilla E, Moro D, Gazzeri S, Brichon PY, Nagy-Mignotte H, Morel F, Jacrot M, Brambilla C (1991) Cytotoxic chemotherapy induces cell differentiation in small-cell lung carcinoma. J Clin Oncol 9: 50–61.PubMed
127.
go back to reference Pleasance ED, Stephens PJ, O’Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, Varela I, Nik-Zainal S, Davies HR, Ordonez GR, Mudie LJ, Latimer C, Edkins S, Stebbings L, Chen L, Jia M, Leroy C, Marshall J, Menzies A, Butler A, Teague JW, Mangion J, Sun YA, McLaughlin SF, Peckham HE, Tsung EF, Costa GL, Lee CC, Minna JD, Gazdar A, Birney E, Rhodes MD, McKernan KJ, Stratton MR, Futreal PA, Campbell PJ (2010) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463: 184–190.PubMedCentralPubMed Pleasance ED, Stephens PJ, O’Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, Varela I, Nik-Zainal S, Davies HR, Ordonez GR, Mudie LJ, Latimer C, Edkins S, Stebbings L, Chen L, Jia M, Leroy C, Marshall J, Menzies A, Butler A, Teague JW, Mangion J, Sun YA, McLaughlin SF, Peckham HE, Tsung EF, Costa GL, Lee CC, Minna JD, Gazdar A, Birney E, Rhodes MD, McKernan KJ, Stratton MR, Futreal PA, Campbell PJ (2010) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463: 184–190.PubMedCentralPubMed
128.
go back to reference George J, Peifer M, Fernandez-Cuesta L, Thomas RK. Comprehensive genome and transcriptome analyses on small cell lung cancer (abstract #1542). AACR Annual Meeting of the American Association of Cancer Research. San Diego (CA); 2014. George J, Peifer M, Fernandez-Cuesta L, Thomas RK. Comprehensive genome and transcriptome analyses on small cell lung cancer (abstract #1542). AACR Annual Meeting of the American Association of Cancer Research. San Diego (CA); 2014.
129.
go back to reference Coe BP, Lee EH, Chi B, Girard L, Minna JD, Gazdar AF, Lam S, MacAulay C, Lam WL (2006) Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines. Genes Chromosomes Cancer 45: 11–19.PubMed Coe BP, Lee EH, Chi B, Girard L, Minna JD, Gazdar AF, Lam S, MacAulay C, Lam WL (2006) Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines. Genes Chromosomes Cancer 45: 11–19.PubMed
Metadata
Title
Unraveling Tumor Grading and Genomic Landscape in Lung Neuroendocrine Tumors
Authors
Giuseppe Pelosi
Mauro Papotti
Guido Rindi
Aldo Scarpa
Publication date
01-06-2014
Publisher
Springer US
Published in
Endocrine Pathology / Issue 2/2014
Print ISSN: 1046-3976
Electronic ISSN: 1559-0097
DOI
https://doi.org/10.1007/s12022-014-9320-0

Other articles of this Issue 2/2014

Endocrine Pathology 2/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.