Skip to main content
Top
Published in: Tumor Biology 5/2014

01-05-2014 | Research Article

Relationship of immunohistochemical biomarker expression and lymph node involvement in patients undergoing surgical treatment of NSCLC with long-term follow-up

Authors: Ana María Gómez, Jose Ramón Jarabo Sarceda, Jose Antonio L. García-Asenjo, Cristina Fernandez, Susana Hernandez, Julian Sanz, Elena Fernandez, Joaquin Calatayud, Antonio Torres, Florentino Hernando

Published in: Tumor Biology | Issue 5/2014

Login to get access

Abstract

We try to identify the relationship between immunohistochemical marker expression and lymph node involvement in a cohort of 282 patients followed for 5 years after curative resection for NSCLC. In 189 patients (67 %), lymph nodes were unaffected while 93 patients (33 %) showed nodal involvement. The expression of 15 molecular markers was determined from each patient by tissue-array immunohistochemistry. Univariate analysis indicated significantly higher expression of E-cadherin, γ-catenin, p27, and p53 in patients with lymph node involvement. In those with unaffected nodes, p16 and Rb were expressed. E-cadherin expression was related to a 50 % mortality reduction in patients with node involvement (hazard ratio (HR) 0.5; p = 0.017). c-erbB-2 expression was correlated with a 3.4-fold increase in mortality compared to patients without expression of this marker in subjects without node involvement (HR 3.41; p = 0.017). Multivariate analysis identified c-erbB-2 (HR 2.22; p = 0.089) and p27 (HR 1.44; p = 0.019) as prognostics of mortality while Rb (HR 0.74) indicated a good prognosis. The expression of proteins encoded by oncogenes and tumor suppressor genes was different according to lymph node involvement. The increased mortality related to c-erbB-2 expression in patients with unaffected lymph nodes would suggests a need for adjuvant treatment.
Literature
1.
go back to reference Grossi F, Spizzo R, Bordo D, et al. Prognostic stratification of stage IIIA pN2 non-small cell lung cancer by hierarchical clustering analysis of tissue microarray immunostaining data. J Thorac Oncol. 2010;5:1354–60.CrossRefPubMed Grossi F, Spizzo R, Bordo D, et al. Prognostic stratification of stage IIIA pN2 non-small cell lung cancer by hierarchical clustering analysis of tissue microarray immunostaining data. J Thorac Oncol. 2010;5:1354–60.CrossRefPubMed
2.
go back to reference Yokoi S, Yasui K, Mori M, et al. Amplification and overexpression of skp2 are associated with metastasis of non-small-cell lung cancers to lymph nodes. Am J Pathol. 2004;165:175–80.CrossRefPubMedPubMedCentral Yokoi S, Yasui K, Mori M, et al. Amplification and overexpression of skp2 are associated with metastasis of non-small-cell lung cancers to lymph nodes. Am J Pathol. 2004;165:175–80.CrossRefPubMedPubMedCentral
3.
go back to reference Moriya Y, Iyoda A, Kasai Y, et al. Prediction of lymph node metastasis by gene expression profiling in patients with primary resected lung cancer. Lung Cancer. 2009;64:86–91.CrossRefPubMed Moriya Y, Iyoda A, Kasai Y, et al. Prediction of lymph node metastasis by gene expression profiling in patients with primary resected lung cancer. Lung Cancer. 2009;64:86–91.CrossRefPubMed
4.
go back to reference Brambilla C, Fievet F, Jeanmart M, et al. Early detection of lung cancer: role of biomarkers. Eur Respir J. 2003;21(Suppl39):36s–44.CrossRef Brambilla C, Fievet F, Jeanmart M, et al. Early detection of lung cancer: role of biomarkers. Eur Respir J. 2003;21(Suppl39):36s–44.CrossRef
5.
go back to reference Grupo de Trabajo de la SEPAR Normativa actualizada. Sobre diagnóstico y estadificación del carcinoma broncogénico. Arch Bronconeumol. 1998;34:437–52.CrossRef Grupo de Trabajo de la SEPAR Normativa actualizada. Sobre diagnóstico y estadificación del carcinoma broncogénico. Arch Bronconeumol. 1998;34:437–52.CrossRef
6.
go back to reference Rami-Porta R, Mateu-Navarro M, Freixinet J, et al. Type of resection and prognosis in lung cancer. Experience of a multicentre study. Eur J Cardiothorac Surg. 2005;28:622–8.CrossRefPubMed Rami-Porta R, Mateu-Navarro M, Freixinet J, et al. Type of resection and prognosis in lung cancer. Experience of a multicentre study. Eur J Cardiothorac Surg. 2005;28:622–8.CrossRefPubMed
7.
go back to reference Fernández E. Estudios epidemiologicos (STROBE). Med Clin (Barc). 2005;125:43–8.CrossRef Fernández E. Estudios epidemiologicos (STROBE). Med Clin (Barc). 2005;125:43–8.CrossRef
8.
go back to reference Bria E, Milella M, Sperduti I, et al. A novel clinical prognostic score incorporating the number of resected lymph-nodes to predict recurrence and survival in non-small-cell lung cancer. Lung Cancer. 2009;66:365–71.CrossRefPubMed Bria E, Milella M, Sperduti I, et al. A novel clinical prognostic score incorporating the number of resected lymph-nodes to predict recurrence and survival in non-small-cell lung cancer. Lung Cancer. 2009;66:365–71.CrossRefPubMed
9.
go back to reference Lee JG, Lee CY, Park IK, et al. Number of metastatic lymph nodes in resected non-small cell lung cancer predicts patient survival. Ann Thorac Surg. 2008;85:211–5.CrossRefPubMed Lee JG, Lee CY, Park IK, et al. Number of metastatic lymph nodes in resected non-small cell lung cancer predicts patient survival. Ann Thorac Surg. 2008;85:211–5.CrossRefPubMed
10.
go back to reference Lardinois D, Suter H, Hakki H, et al. Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer. Ann Thorac Surg. 2005;80:268–75.CrossRefPubMed Lardinois D, Suter H, Hakki H, et al. Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer. Ann Thorac Surg. 2005;80:268–75.CrossRefPubMed
11.
go back to reference Bollen E, Van Duin CJ, Theunissen PHMH, et al. Mediastinal lymph node dissection in resected lung cancer: morbidity and accuracy of staging. Ann Thorac Surg. 1993;55:961–6.CrossRefPubMed Bollen E, Van Duin CJ, Theunissen PHMH, et al. Mediastinal lymph node dissection in resected lung cancer: morbidity and accuracy of staging. Ann Thorac Surg. 1993;55:961–6.CrossRefPubMed
12.
go back to reference Singhal S, Vachani A, Antin-Ozerkis D, et al. Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 2005;11:3974–86.CrossRefPubMed Singhal S, Vachani A, Antin-Ozerkis D, et al. Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 2005;11:3974–86.CrossRefPubMed
13.
go back to reference Baldi A, Esposito V, De Luca A, et al. Differential expression of the retinoblastoma gene family members pRb/p105, p107, and pRb2/p130 in lung cancer. Clin Cancer Res. 1996;2:1239–45.PubMed Baldi A, Esposito V, De Luca A, et al. Differential expression of the retinoblastoma gene family members pRb/p105, p107, and pRb2/p130 in lung cancer. Clin Cancer Res. 1996;2:1239–45.PubMed
14.
go back to reference Caputi M, Groeger AM, Esposito V, et al. Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer. Clin Cancer Res. 2002;8:3850–6.PubMed Caputi M, Groeger AM, Esposito V, et al. Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer. Clin Cancer Res. 2002;8:3850–6.PubMed
15.
go back to reference Catzavelos C, Tsao MS, DeBoer G, et al. Reduced expression of the cell cycle inhibitor p27Kip1 in non-small cell lung carcinoma: a prognostic factor independent of Ras. Cancer Res. 1999;59:684–8.PubMed Catzavelos C, Tsao MS, DeBoer G, et al. Reduced expression of the cell cycle inhibitor p27Kip1 in non-small cell lung carcinoma: a prognostic factor independent of Ras. Cancer Res. 1999;59:684–8.PubMed
16.
go back to reference Cheng YL, Lee SC, Harn H-J, et al. Prognostic prediction of the immunohistochemical expression of p53 and p16 in resected non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23:221–8.CrossRefPubMed Cheng YL, Lee SC, Harn H-J, et al. Prognostic prediction of the immunohistochemical expression of p53 and p16 in resected non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23:221–8.CrossRefPubMed
17.
18.
go back to reference Hayashi H, Ogawa N, Ishiwa N, et al. High cyclin E and low p27/Kip1 expressions are potentially poor prognostic factors in lung adenocarcinoma patients. Lung Cancer. 2001;34:59–65.CrossRefPubMed Hayashi H, Ogawa N, Ishiwa N, et al. High cyclin E and low p27/Kip1 expressions are potentially poor prognostic factors in lung adenocarcinoma patients. Lung Cancer. 2001;34:59–65.CrossRefPubMed
19.
go back to reference Kawasaki M, Nakanishi Y, Kuwano K, et al. The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer. Clin Cancer Res. 1997;3:1195–200.PubMed Kawasaki M, Nakanishi Y, Kuwano K, et al. The utility of p53 immunostaining of transbronchial biopsy specimens of lung cancer: p53 overexpression predicts poor prognosis and chemoresistance in advanced non-small cell lung cancer. Clin Cancer Res. 1997;3:1195–200.PubMed
20.
go back to reference Sanchez PA, Torres AJ, Iniesta P, et al. Prognostic significance of p53 gene mutations in squamous cell carcinoma of the lung. Oncol R. 1998;5:1129–33. Sanchez PA, Torres AJ, Iniesta P, et al. Prognostic significance of p53 gene mutations in squamous cell carcinoma of the lung. Oncol R. 1998;5:1129–33.
21.
go back to reference Tong J, Sun X, Cheng H, et al. Expression of p16 in non-small cell lung cancer and its prognostic significance: a meta-analysis of published literatures Review Article. Lung Cancer. 2011;74:155–63.CrossRefPubMed Tong J, Sun X, Cheng H, et al. Expression of p16 in non-small cell lung cancer and its prognostic significance: a meta-analysis of published literatures Review Article. Lung Cancer. 2011;74:155–63.CrossRefPubMed
22.
go back to reference Gorgoulis VG, Zacharatos P, Kotsinas A, et al. Alterations of the p16-pRb pathway and the chromosome locus 9p21–22 in non-small-cell lung carcinomas: relationship with p53 and MDM2 protein expression. Am J Pathol. 1998;153:1749–65.CrossRefPubMedPubMedCentral Gorgoulis VG, Zacharatos P, Kotsinas A, et al. Alterations of the p16-pRb pathway and the chromosome locus 9p21–22 in non-small-cell lung carcinomas: relationship with p53 and MDM2 protein expression. Am J Pathol. 1998;153:1749–65.CrossRefPubMedPubMedCentral
23.
go back to reference Baldi A, De Luca A, Esposito V. et al. Tumor suppressors and cell-cycle proteins in lung cancer. Review article. Pathology Research International 2011;1-12 Baldi A, De Luca A, Esposito V. et al. Tumor suppressors and cell-cycle proteins in lung cancer. Review article. Pathology Research International 2011;1-12
24.
go back to reference Esposito V, Baldi A, DeLuca A, et al. Prognostic role of the cyclin-dependent kinase Inhibitor p27 in non-small cell lung cancer. Cancer Res. 1997;57:3381–5.PubMed Esposito V, Baldi A, DeLuca A, et al. Prognostic role of the cyclin-dependent kinase Inhibitor p27 in non-small cell lung cancer. Cancer Res. 1997;57:3381–5.PubMed
25.
go back to reference Kaye FJ. RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer. Oncogene. 2002;21:6908–14.CrossRefPubMed Kaye FJ. RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer. Oncogene. 2002;21:6908–14.CrossRefPubMed
26.
go back to reference Lloyd RV, Erickson LA, Jin L, et al. p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol. 1999;154:313–23.CrossRefPubMedPubMedCentral Lloyd RV, Erickson LA, Jin L, et al. p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol. 1999;154:313–23.CrossRefPubMedPubMedCentral
27.
go back to reference Schneider PM, Praeuer HW, Stoeltzing O, et al. Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer. Br J Cancer. 2000;83:473–9.CrossRefPubMedPubMedCentral Schneider PM, Praeuer HW, Stoeltzing O, et al. Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer. Br J Cancer. 2000;83:473–9.CrossRefPubMedPubMedCentral
28.
go back to reference Grob TJ, Kannengiesser I, Tsourlakis MC, et al. Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung. Mod Pathol. 2012;25(12):1566–73.CrossRefPubMed Grob TJ, Kannengiesser I, Tsourlakis MC, et al. Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung. Mod Pathol. 2012;25(12):1566–73.CrossRefPubMed
29.
go back to reference Cantero R, Torres AJ, Maestro ML, et al. Pronostic value of the quantified expression of p185 in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2000;119:1119–25.CrossRefPubMed Cantero R, Torres AJ, Maestro ML, et al. Pronostic value of the quantified expression of p185 in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2000;119:1119–25.CrossRefPubMed
30.
go back to reference Díez M, Pollan M, Maestro M, et al. Prediction of recurrence by quantification of p185 protein in non-small cell lung cancer tissue. Br J Cancer. 1997;75:684–9.CrossRefPubMedPubMedCentral Díez M, Pollan M, Maestro M, et al. Prediction of recurrence by quantification of p185 protein in non-small cell lung cancer tissue. Br J Cancer. 1997;75:684–9.CrossRefPubMedPubMedCentral
31.
go back to reference Shi D, He G, Cao S, et al. Overexpression of the c-erbB-2/neu–encoded p185 protein in primary lung cancer. Mol Carcinog. 1992;5:213–8.CrossRefPubMed Shi D, He G, Cao S, et al. Overexpression of the c-erbB-2/neu–encoded p185 protein in primary lung cancer. Mol Carcinog. 1992;5:213–8.CrossRefPubMed
32.
go back to reference Micke P, Basrai M, Faldum A, et al. Characterization of c-kit expression in small cell lung cancer: prognostic and therapeutic implications. Clin Cancer Res. 2003;9:188–94.PubMed Micke P, Basrai M, Faldum A, et al. Characterization of c-kit expression in small cell lung cancer: prognostic and therapeutic implications. Clin Cancer Res. 2003;9:188–94.PubMed
33.
go back to reference Meert AP, Martin B, Delmotte P, et al. The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis. Eur Respir J. 2002;20:975–81.CrossRefPubMed Meert AP, Martin B, Delmotte P, et al. The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis. Eur Respir J. 2002;20:975–81.CrossRefPubMed
34.
go back to reference Gosney JR, Field JK, Gosney MA, et al. c-myc oncoprotein in bronchial carcinoma: expression in all major morphological types. Anticancer Res. 1990;10:623–8.PubMed Gosney JR, Field JK, Gosney MA, et al. c-myc oncoprotein in bronchial carcinoma: expression in all major morphological types. Anticancer Res. 1990;10:623–8.PubMed
35.
go back to reference Barr LF, Campbell SE, Diette GB. c-Myc Suppresses the tumorigenicity of lung cancer cells and down-regulates vascular endothelial growth factor expression. Cancer Res. 2000;60:143–9.PubMed Barr LF, Campbell SE, Diette GB. c-Myc Suppresses the tumorigenicity of lung cancer cells and down-regulates vascular endothelial growth factor expression. Cancer Res. 2000;60:143–9.PubMed
36.
go back to reference Liu D, Huang C, Kameyama K, et al. E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer. Ann Thorac Surg. 2001;71:949–55.CrossRefPubMed Liu D, Huang C, Kameyama K, et al. E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer. Ann Thorac Surg. 2001;71:949–55.CrossRefPubMed
37.
go back to reference Böhm J, Niskanen L, Kiraly K, et al. Expression and prognostic value of α-, β-, and γ-catenins in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2000;85:4806–11.PubMed Böhm J, Niskanen L, Kiraly K, et al. Expression and prognostic value of α-, β-, and γ-catenins in differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2000;85:4806–11.PubMed
38.
go back to reference Choi YS, Shim YM, Kim SH, et al. Prognostic significance of E-cadherin and ß-catenin in resected stage I non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;24:441–9.CrossRefPubMed Choi YS, Shim YM, Kim SH, et al. Prognostic significance of E-cadherin and ß-catenin in resected stage I non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;24:441–9.CrossRefPubMed
39.
go back to reference Kase S, Sugio K, Yamazaki K, et al. Expression of E-cadherin and b-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res. 2000;6:4789–96.PubMed Kase S, Sugio K, Yamazaki K, et al. Expression of E-cadherin and b-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res. 2000;6:4789–96.PubMed
40.
go back to reference Kimura K, Endo Y, Yonemyra Y, et al. Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer. Int J Oncol. 2000;16:1125–31.PubMed Kimura K, Endo Y, Yonemyra Y, et al. Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer. Int J Oncol. 2000;16:1125–31.PubMed
41.
go back to reference Nozawa N, Hashimoto S, Nakashima Y, et al. Immunohistochemical α- and β-catenin and E-cadherin expression and their clinicopathological significance in human lung adenocarcinoma. Pathol-Res Pract. 2006;202:639–50.CrossRefPubMed Nozawa N, Hashimoto S, Nakashima Y, et al. Immunohistochemical α- and β-catenin and E-cadherin expression and their clinicopathological significance in human lung adenocarcinoma. Pathol-Res Pract. 2006;202:639–50.CrossRefPubMed
42.
go back to reference Bröker LE, Huisman C, Span SW, et al. Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells. Cancer Res. 2004;64:27–30.CrossRefPubMed Bröker LE, Huisman C, Span SW, et al. Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells. Cancer Res. 2004;64:27–30.CrossRefPubMed
43.
go back to reference Esposito V, Baldi A, De Luca A, et al. Cell cycle related proteins as prognostic parameters in radically resected non-small cell lung cancer. J Clin Pathol. 2005;58:734–9.CrossRefPubMedPubMedCentral Esposito V, Baldi A, De Luca A, et al. Cell cycle related proteins as prognostic parameters in radically resected non-small cell lung cancer. J Clin Pathol. 2005;58:734–9.CrossRefPubMedPubMedCentral
44.
go back to reference Hommura F, Dosaka-Akita H, Kinoshita I, et al. Predictive value of expression of p16INK4A, retinoblastoma and p53 proteins for the prognosis of non-small-cell lung cancers. Br J Cancer. 1999;81:696–701.CrossRefPubMedPubMedCentral Hommura F, Dosaka-Akita H, Kinoshita I, et al. Predictive value of expression of p16INK4A, retinoblastoma and p53 proteins for the prognosis of non-small-cell lung cancers. Br J Cancer. 1999;81:696–701.CrossRefPubMedPubMedCentral
45.
go back to reference Takada M, Tada M, Tamoto E, et al. Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer. J Surg Res. 2004;122:61–9.CrossRefPubMed Takada M, Tada M, Tamoto E, et al. Prediction of lymph node metastasis by analysis of gene expression profiles in non-small cell lung cancer. J Surg Res. 2004;122:61–9.CrossRefPubMed
46.
go back to reference Donnem T, Lonvik K, Eklo K, et al. Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer: coexpression with vascular endothelial growth factor-A predicts poor survival.n2011;117:3193-3200 Donnem T, Lonvik K, Eklo K, et al. Independent and tissue-specific prognostic impact of miR-126 in nonsmall cell lung cancer: coexpression with vascular endothelial growth factor-A predicts poor survival.n2011;117:3193-3200
47.
go back to reference Zhu CQ, Shih W, Ling C-H, et al. Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol. 2006;59:790–800.CrossRefPubMedPubMedCentral Zhu CQ, Shih W, Ling C-H, et al. Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol. 2006;59:790–800.CrossRefPubMedPubMedCentral
48.
go back to reference Bremnes RM, Veve R, Gabrielson E, et al. High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. JCO. 2002;20:2417–28.CrossRef Bremnes RM, Veve R, Gabrielson E, et al. High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. JCO. 2002;20:2417–28.CrossRef
49.
go back to reference Sulzer MA, Leers MPG, van Noord JA, et al. Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in nonsmall cell lung cancer. Am J Respir Crit Care Med. 1998;157:1319–23.CrossRefPubMed Sulzer MA, Leers MPG, van Noord JA, et al. Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in nonsmall cell lung cancer. Am J Respir Crit Care Med. 1998;157:1319–23.CrossRefPubMed
50.
go back to reference Ucvet A, Kul C, Gursoy S, et al. Valor pronóstico del receptor del factor de crecimiento epitelial, factor de crecimiento endotelial vascular, E-cadherina, y p120 catenina en el carcinoma de pulmón no microcítico resecado. Arch Bronconeumol. 2011;47:397–402.CrossRefPubMed Ucvet A, Kul C, Gursoy S, et al. Valor pronóstico del receptor del factor de crecimiento epitelial, factor de crecimiento endotelial vascular, E-cadherina, y p120 catenina en el carcinoma de pulmón no microcítico resecado. Arch Bronconeumol. 2011;47:397–402.CrossRefPubMed
51.
go back to reference Nakashima T, Huang C, Liu D, et al. Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients. Br J Cancer. 2003;88:1727–33.CrossRefPubMedPubMedCentral Nakashima T, Huang C, Liu D, et al. Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients. Br J Cancer. 2003;88:1727–33.CrossRefPubMedPubMedCentral
52.
go back to reference Mohamed S, Yasufuku K, Hiroshima K, et al. Prognostic implications of cell cycle-related proteins in primary resectable pathologic N2 non-small cell lung cancer. Cancer. 2007;109:2506–14.CrossRefPubMed Mohamed S, Yasufuku K, Hiroshima K, et al. Prognostic implications of cell cycle-related proteins in primary resectable pathologic N2 non-small cell lung cancer. Cancer. 2007;109:2506–14.CrossRefPubMed
53.
go back to reference Sterlacci W, Tzankov A, Veits L, et al. A comprehensive analysis of p16 expression, gene status, and promoter hypermethylation in surgically resected non-small cell lung carcinomas. J Thorac Oncol. 2011;6:1649–57.CrossRefPubMed Sterlacci W, Tzankov A, Veits L, et al. A comprehensive analysis of p16 expression, gene status, and promoter hypermethylation in surgically resected non-small cell lung carcinomas. J Thorac Oncol. 2011;6:1649–57.CrossRefPubMed
54.
go back to reference Sion-Vardy N, Freedman J, Lazarov I, et al. p27kip1 expression in non-small cell lung cancer is not an independent prognostic factor. Anticancer Res. 2010;30:3699–704.PubMed Sion-Vardy N, Freedman J, Lazarov I, et al. p27kip1 expression in non-small cell lung cancer is not an independent prognostic factor. Anticancer Res. 2010;30:3699–704.PubMed
55.
go back to reference Cheng YL, Lee SC, Harn HJ, et al. Prognostic prediction of the immunohistochemical expression of p53 and p16 in resected non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23:221–8.CrossRefPubMed Cheng YL, Lee SC, Harn HJ, et al. Prognostic prediction of the immunohistochemical expression of p53 and p16 in resected non-small cell lung cancer. Eur J Cardiothorac Surg. 2003;23:221–8.CrossRefPubMed
56.
go back to reference Esposito V, Deluca A, Baldi A, et al. Altered expression of p53 and Rb tumor suppressor genes in lung cancer: relationship with survival. Int J Oncol. 1996;9:439–43.PubMed Esposito V, Deluca A, Baldi A, et al. Altered expression of p53 and Rb tumor suppressor genes in lung cancer: relationship with survival. Int J Oncol. 1996;9:439–43.PubMed
57.
go back to reference Au NH, Cheang M, Huntsman DG, et al. Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. J Pathol. 2004;204:101–9.CrossRefPubMed Au NH, Cheang M, Huntsman DG, et al. Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. J Pathol. 2004;204:101–9.CrossRefPubMed
Metadata
Title
Relationship of immunohistochemical biomarker expression and lymph node involvement in patients undergoing surgical treatment of NSCLC with long-term follow-up
Authors
Ana María Gómez
Jose Ramón Jarabo Sarceda
Jose Antonio L. García-Asenjo
Cristina Fernandez
Susana Hernandez
Julian Sanz
Elena Fernandez
Joaquin Calatayud
Antonio Torres
Florentino Hernando
Publication date
01-05-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1599-9

Other articles of this Issue 5/2014

Tumor Biology 5/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine