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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

Clinical validation of the gastrointestinal NET grading system: Ki67 index criteria of the WHO 2010 classification is appropriate to predict metastasis or recurrence

Published in: Diagnostic Pathology | Issue 1/2013

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Abstract

Background

In the WHO 2010 classification, the neuroendocrine tumors (NETs) are subdivided by their mitotic index or Ki67 index into either G1 or G2 NETs. Tumors with a Ki67 index of <2% are classified as G1 and those with 3—20% are classified as G2. However, the assessment of tumors with Ki67 index of greater than 2% and less than or equal to 3% is still unclear. To resolve the problem, we validated the Ki67 index criteria of gastrointestinal NETs of the WHO 2010 classification.

Methods

The medical records of 45 patients who were pathologically diagnosed as having NET G1/G2 of the gastrointestinal tract were analyzed retrospectively. According to the WHO 2010 classification, Ki67 index were calculated. Computer-assisted cytometrical analysis of Ki67 immunoreactivity was performed using the WinRooF image processing software. Receiver operating characteristic (ROC) curves were generated to determine the best discriminating Ki67 index. To clarify the assessment of tumors with Ki67 index between 2—3%, the calculated cutoff of Ki67 index was evaluated using Fisher’s exact test.

Results

ROC curve analysis confirmed that 2.8% was the best Ki67 index cutoff value for predicting metastasis or recurrence. The sensitivity of the new Ki67 index cutoff was 42.9%, and the specificity was 86.8%.

Conclusions

Division of NETs into G1/G2 based on Ki67 index of 3% was appropriate to predict metastases or recurrences. The WHO grading system may be the most useful classification to predict metastases or recurrences.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​1553036118943799​
Appendix
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Literature
1.
Oberndorfer S: Karzinoide tumoren des dunndarms. Frankf Z Pathol. 1907, 1: 426-432.
2.
Modlin IM, Shapiro MD, Kidd M: Siegfried Oberndorfer: origins and perspectives of carcinoid tumors. Hum Pathol. 2004, 35: 1440-1451.CrossRefPubMed
3.
Pearse AG: The diffuse endocrine system and the implications of the APUD concept. Int Surg. 1979, 64: 5-7.PubMed
4.
Pearse AG, McConnell DG: Cytochemical localization of redox compounds in isolated bovine retinal outer segment disks. Nature. 1966, 212: 1367-1368.CrossRefPubMed
5.
Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P: TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006, 449: 395-401.PubMedCentralCrossRefPubMed
6.
Rindi G, Kloppel G, Couvelard A, Komminoth P, Korner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A: TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007, 451: 757-762.CrossRefPubMed
7.
Rindi G, Arnold R, Bosman F, Capella C, Klimstra D, Klöppel G, Komminoth P, Solcia E: Nomenclature and classification of neuroendocrine neoplasms of the digestive system. WHO Classification of Tumours of the Digestive System. Edited by: Bosman F, Carneiro F, Hruban R, Theise N. 2010, Lyon: International Agency for Research on Cancer, 13-14. 4
8.
Pape UF, Jann H, Muller-Nordhorn J, Bockelbrink A, Berndt U, Willich SN, Koch M, Rocken C, Rindi G, Wiedenmann B: Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer. 2008, 113: 256-265.CrossRefPubMed
9.
Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gonen M, Jensen RT, Kidd M, Kulke MH, Lloyd RV: Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol. 2010, 34: 300-313.CrossRefPubMed
10.
Kloppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, Scarpa A, Scoazec JY, Wiedenmann B, Papotti M: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology. 2009, 90: 162-166.CrossRefPubMed
11.
Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S: Gastrointestinal stromal tumor: Consistent CD117 immunostaining for diagnosis, and prognostic classification based on tumor size and MIB-1 grade. Hum Pathol. 2002, 33: 669-676.CrossRefPubMed
12.
Fujimori Y, Fujimori T, Imura J, Sugai T, Yao T, Wada R, Ajioka Y, Ohkura Y: An assessment of the diagnostic criteria for sessile serrated adenoma/polyps: SSA/Ps using image processing software analysis for Ki67 immunohistochemistry. Diagn Pathol. 2012, 7: 59-PubMedCentralPubMed
13.
Shida Y, Ichikawa K, Fujimori T: Differentiation between sessile serrated adenoma/polyp and non-sessile serrated adenoma/polyp in large hyper plastic polyp: A Japanese collaborative study. Mol Clin Oncol. 2013, 1: 53-58.PubMedCentralPubMed
14.
Lee SM, Ahn S, Lee YK, Jang KT, Park CK, Kim KM: Neuroendocrine tumor in gastric adenoma: a diagnostic pitfall mimicking invasive adenocarcinoma. Diagn Pathol. 2012, 7: 102-PubMedCentralCrossRefPubMed
15.
Kimura T, Fukui H, Sekikawa A, Yamagishi H, Ichikawa K, Tomita S, Fujii S, Imura J, Kawamata H, Chiba T: Involvement of REG Ialpha protein in the regeneration of ductal epithelial cells in the minor salivary glands of patients with Sjogren's syndrome. Clin Exp Immunol. 2009, 155: 16-20.PubMedCentralCrossRefPubMed
16.
Kusaka T, Fukui H, Sano Y, Ueda Y, Chiba T, Fujimori T: Analysis of K-ras codon 12 mutations and p53 overexpression in colorectal nodule-aggregating tumors. J Gastroenterol Hepatol. 2000, 15: 1151-1157.CrossRefPubMed
17.
Kayser K, Schultz H, Goldmann T, Gortler J, Kayser G, Vollmer E: Theory of sampling and its application in tissue based diagnosis. Diagn Pathol. 2009, 4: 6-PubMedCentralCrossRefPubMed
18.
Belhomme P, Oger M, Michels JJ, Plancoulaine B, Herlin P: Towards a computer aided diagnosis system dedicated to virtual microscopy based on stereology sampling and diffusion maps. Diagn Pathol. 2011, 6 (Suppl 1): S3-PubMedCentralCrossRefPubMed
19.
20.
Hatanaka Y, Hashizume K, Nitta K, Kato T, Itoh I, Tani Y: Cytometrical image analysis for immunohistochemical hormone receptor status in breast carcinomas. Pathol Int. 2003, 53: 693-699.CrossRefPubMed
21.
Tang LH, Gonen M, Hedvat C, Modlin IM, Klimstra DS: Objective quantification of the Ki67 proliferative index in neuroendocrine tumors of the gastroenteropancreatic system: a comparison of digital image analysis with manual methods. Am J Surg Pathol. 2012, 36: 1761-1770.CrossRefPubMed
22.
Konsti J, Lundin M, Linder N, Haglund C, Blomqvist C, Nevanlinna H, Aaltonen K, Nordling S, Lundin J: Effect of image compression and scaling on automated scoring of immunohistochemical stainings and segmentation of tumor epithelium. Diagn Pathol. 2012, 7: 29-PubMedCentralCrossRefPubMed
23.
Biggerstaff BJ: Comparing diagnostic tests: a simple graphic using likelihood ratios. Stat Med. 2000, 19: 649-663.CrossRefPubMed
24.
Zhang ML, Gao YX, Wang X, Chang H, Huang GW: Serum uric acid and appropriate cutoff value for prediction of metabolic syndrome among Chinese adults. J Clin Biochem Nutr. 2013, 52: 38-42.PubMedCentralCrossRefPubMed
25.
Dogan H, Hot I: Contributions of Siegfried Oberndorfer to pathology and evolution of carcinoid. Pol J Pathol. 2010, 61: 49-53.PubMed
26.
Kasuga A, Chino A, Uragami N, Kishihara T, Igarashi M, Fujita R, Yamamoto N, Ueno M, Oya M, Muto T: Treatment strategy for rectal carcinoids: a clinicopathological analysis of 229 cases at a single cancer institution. J Gastroenterol Hepatol. 2012, 27: 1801-1807.CrossRefPubMed
27.
Modlin IM, Moss SF, Chung DC, Jensen RT, Snyderwine E: Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors. J Natl Cancer Inst. 2008, 100: 1282-1289.PubMedCentralCrossRefPubMed
28.
29.
Andrew A, Kramer B, Rawdon BB: The origin of gut and pancreatic neuroendocrine (APUD) cells–the last word?. J Pathol. 1998, 186: 117-118.CrossRefPubMed
30.
Hosoda S, Kito H, Nogaki M, Masumori S, Ito S: Is rectal carcinoid argyrophilic? Application of Grimelius' silver nitrate stain in four cases. Dis Colon Rectum. 1975, 18: 386-390.CrossRefPubMed
31.
Kito H, Hosoda S: Triple staining for simultaneous visualization of cell types in islet of Langerhans of pancreas. Successive application of argyrophil, aldehyde-fuchsin and lead-hematoxylin stains in a single tissue section. J Histochem Cytochem. 1977, 25: 1019-1020.CrossRefPubMed
32.
Soga J: Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases. Cancer. 2005, 103: 1587-1595.CrossRefPubMed
33.
Soga J, Tazawa K: Pathologic analysis of carcinoids. Histologic reevaluation of 62 cases. Cancer. 1971, 28: 990-998.CrossRefPubMed
34.
Niederle MB, Hackl M, Kaserer K, Niederle B: Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer. 2010, 17: 909-918.CrossRefPubMed
35.
Ferrone CR, Tang LH, Tomlinson J, Gonen M, Hochwald SN, Brennan MF, Klimstra DS, Allen PJ: Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified?. J Clin Oncol. 2007, 25: 5609-5615.CrossRefPubMed
36.
Khan MS, Kirkwood A, Tsigani T, Garcia-Hernandez J, Hartley JA, Caplin ME, Meyer T: Circulating tumor cells as prognostic markers in neuroendocrine tumors. J Clin Oncol. 2013, 31: 365-372.CrossRefPubMed
37.
Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh KH, Yu W, Xiao W, Davis MM, Pease RF, Mindrinos MN: Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci U S A. 2009, 106: 3970-3975.PubMedCentralCrossRefPubMed
Metadata
Title
Clinical validation of the gastrointestinal NET grading system: Ki67 index criteria of the WHO 2010 classification is appropriate to predict metastasis or recurrence
Publication date
01-12-2013
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-65

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