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Abnormal Expression of p16 INK4a , Cyclin D1, Cyclin‐Dependent Kinase 4 and Retinoblastoma Protein in Gastric Carcinomas
Author(s) -
Kishimoto Ichiro,
Mitomi Hiroyuki,
Ohkura Yasuo,
Kanazawa Hideki,
Fukui Naoshi,
Watanabe Masahiko
Publication year - 2008
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21087
Subject(s) - cyclin d1 , retinoblastoma protein , retinoblastoma , cancer research , immunohistochemistry , cyclin dependent kinase , cell cycle , medicine , cyclin b , cyclin , cyclin dependent kinase 4 , pathology , biology , cancer , cyclin dependent kinase 2 , gene , genetics
Background and Objectives The p16 INK4a (p16), cyclin D1, cyclin‐dependent kinase (CDK) 4 and retinoblastoma (Rb) genes are components of the Rb pathway that controls the G1‐S checkpoint of the cell cycle. The aim of this study was to assess the relationship between their abnormalities and clinicopathological features in gastric carcinomas. Mehtods Immunohistochemical analysis of the encoded proteins was performed on a series of 158 cases. Results Loss of p16/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively. At least 1 of these abnormalities was found in 86% of the cases and a positive correlation was noted between p16 and pRb ( P = 0.009). Cyclin D1 ( P = 0.042) and CDK4 ( P = 0.008) overexpession was inversely associated with lymph node metastasis and depth of invasion, respectively. Loss of pRb expression was more frequently in diffuse type lesions than in the intestinal type ( P = 0.022). The patients with p16+/pRb−/cyclin D1−/CDK4− or p16−/pRb+/cyclin D1−/CDK4− tumors demonstrated particularly poor survival. With multivariate survival analysis, only depth of invasion and TNM stage could be proven as independent predictors. Conclusions The Rb pathway is disrupted in the vast majority of gastric carcinomas. This study also identified specific immunohistochemical marker profiles for prognosis. J. Surg. Oncol. 2008;98:60–66. © 2008 Wiley‐Liss, Inc.