Ki67-An unsuitable marker of gastric cancer prognosis unmasks intratumoral heterogeneity

Background and Objectives Due to contradictious findings of previous studies regarding Ki67's value in gastric cancer (GC), we reevaluated the expression of Ki67 in whole tissue sections (WTS) and tissue microarrays (TMAs) of GC testing the following hypotheses: does Ki67 show intratumoral hete...

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Bibliographic Details
Published in:Journal of surgical oncology 2016-01, Vol.113 (1), p.46-54
Main Authors: Böger, Christine, Behrens, Hans-Michael, Röcken, Christoph
Format: Article
Language:English
Subjects:
Adenocarcinoma - chemistry
Adenocarcinoma - pathology
Aged
Biomarkers, Tumor - analysis
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Ki-67 Antigen - analysis
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
Phenotype
Predictive Value of Tests
Prognosis
prognostic biomarker
proliferation
Stomach Neoplasms - chemistry
Stomach Neoplasms - pathology
Tissue Array Analysis
tumor heterogeneity
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Summary:Background and Objectives Due to contradictious findings of previous studies regarding Ki67's value in gastric cancer (GC), we reevaluated the expression of Ki67 in whole tissue sections (WTS) and tissue microarrays (TMAs) of GC testing the following hypotheses: does Ki67 show intratumoral heterogeneity; are TMAs representative in the determination of the Ki67 proliferation index (PI); is the Ki67 PI subject to an intralaboratory variability; and is the Ki67 PI related to clinico‐pathological patient characteristics and/or prognostically relevant in GC. Methods Corresponding WTS and TMAs samples from 315 GCs were stained immunohistochemically. The Ki67 PI evaluated on WTS was correlated with the Ki67 PI evaluated on TMAs, sample age, clinico‐pathological characteristics, and patient survival. Results The overall amount of Ki67‐positive tumor cells did not depend on sample age. Three distinct, partly heterogeneous Ki67 expression patterns were observed. The mean Ki67 PI evaluated on TMAs differed on average minus 16.9% from the Ki67 PI evaluated on WTS. Ki67 in WTS correlated significantly with the Laurén phenotype and tumor grade, but not with patient survival. Conclusion TMAs carry the risk of a systematic underestimation of the Ki67 PI. Ki67 has no prognostic value in GC but might be a potential indicator of intratumoral heterogeneity. J. Surg. Oncol. 2016;113:46–54. © 2015 The Authors. Journal of Surgical Oncology published by Wiley Periodicals, Inc.
ISSN:0022-4790
1096-9098
DOI:10.1002/jso.24104