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Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: Relevance of cellularity and p27 Kip1
Author(s) -
Nemoto Yuta,
Mikami Tetuo,
Hana Kiyomi,
Kikuchi Shirou,
Kobayashi Nobuyuki,
Watanabe Masahiko,
Okayasu Isao
Publication year - 2006
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2006.02038.x
Subject(s) - cell cycle , cyclin d1 , ki 67 , cyclin , cyclin a , stromal cell , biology , pathology , cancer research , gist , cyclin dependent kinase 2 , medicine , immunohistochemistry , oncology , gastroenterology , cancer
The aim of the present study was to determine whether expression of molecules associated with cell cycle regulation and apoptosis might reflect tumor grade and patients' prognosis of gastrointestinal stromal tumor (GIST). Forty‐nine cases of gastric GIST were divided into three grades; low, intermediate, and high risk. Ki‐67, cyclin A, cyclin D1, cyclin E, p16 Ink4 , p21 Waf1 , p27 Kip1 , cyclin‐dependent kinase (cdk)2, cdk4 and single‐strand DNA (ssDNA) were immunohistochemically stained and assessed. Ki‐67, ssDNA, cyclin A and cdk2 had higher labeling indices (LI) in high‐risk than in low‐risk cases. Cyclin E expression was greater in the intermediate‐ than in the low‐risk grade. On Kaplan–Meier analysis, tumor size, necrosis, cellularity, Ki‐67, ssDNA, and cyclin A LI were significantly correlated with disease‐free survival. Necrosis, cellularity, and Ki‐67 LI were significant as prognostic factors on univariate, and Ki‐67 LI on multivariate Cox hazard tests. Within the high‐risk grade, high cellularity and low p27 Kip1 subgroups had the worst prognosis. The histological grade is related to cell turnover, assessed in terms of Ki‐67, ssDNA, cyclin A, cyclin E, and cdk2 levels. Ki‐67, ssDNA, and cyclin A are useful for prediction of prognosis, with cellularity and p27 Kip1 expression as further prognostic factors in high‐risk cases.