title: Ki67--An unsuitable marker of gastric cancer prognosis unmasks intratumoral heterogeneity.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Böger
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Behrens
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: prognostic biomarker; proliferation; tumor heterogeneity