Kishimoto Ichiro, Mitomi Hiroyuki, Ohkura Yasuo, Kanazawa Hideki, Fukui Naoshi, Watanabe Masahiko
Department of Surgery, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan.
J Surg Oncol. 2008 Jul 1;98(1):60-6. doi: 10.1002/jso.21087.
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.
Immunohistochemical analysis of the encoded proteins was performed on a series of 158 cases.
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.
The Rb pathway is disrupted in the vast majority of gastric carcinomas. This study also identified specific immunohistochemical marker profiles for prognosis.
p16(INK4a)（p16）、细胞周期蛋白D1、细胞周期蛋白依赖性激酶（CDK）4和视网膜母细胞瘤（Rb）基因是Rb通路的组成部分，该通路控制细胞周期的G1-S期检查点。本研究旨在评估它们的异常与胃癌临床病理特征之间的关系。
对158例病例进行了编码蛋白的免疫组织化学分析。
在49%/40%的胃癌中分别观察到p16/Rb蛋白（pRb）表达缺失和细胞周期蛋白D1/CDK4过表达，在37%/37%的胃癌中分别观察到细胞周期蛋白D1/CDK4过表达。86%的病例中至少发现其中一种异常，且p16与pRb之间存在正相关（P = 0.009）。细胞周期蛋白D1（P = 0.042）和CDK4（P = 0.008）过表达分别与淋巴结转移和浸润深度呈负相关。pRb表达缺失在弥漫型病变中比在肠型病变中更常见（P = 0.022）。p16+/pRb-/细胞周期蛋白D1-/CDK4-或p16-/pRb+/细胞周期蛋白D1-/CDK4-肿瘤患者的生存率特别低。多因素生存分析显示，只有浸润深度和TNM分期可被证明是独立的预后预测指标。
绝大多数胃癌中Rb通路被破坏。本研究还确定了用于预后的特定免疫组织化学标志物谱。
