Abnormal expression of p16INK4a, cyclin D1, cyclin-dependent kinase 4 and retinoblastoma protein in gastric carcinomas
Abnormal expression of p16INK4a, cyclin D1, cyclin-dependent kinase 4 and retinoblastoma protein in gastric carcinomas
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DOI：
10.1002/jso.21087
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发表时间：
2008-07-01
影响因子：
2.5
通讯作者：
Watanabe, Masahiko
中科院分区：
文献类型：
--
作者：
Kishimoto, Ichiro;Mitomi, Hiroyuki;Watanabe, Masahiko
背景和目的：p 16(INK4a) (p16)、细胞周期蛋白 D 1、细胞周期蛋白依赖性激酶 (CDK) 4 和视网膜母细胞瘤 (Rb) 基因是控制细胞周期 G1-S 检查点的 Rb 通路的组成部分。本研究的目的是评估胃癌中它们的异常与临床病理特征之间的关系。方法：对一系列 158 例病例进行编码蛋白的免疫组织化学分析。结果：在 49%/40% 和 分别为 37%/37% 的胃癌。 86% 的病例中至少发现其中一种异常，并且 p16 和 pRb 之间存在正相关性 (P = 0.009)。 Cyclin D I (P = 0.042) 和 CDK4 (P = 0.008) 过度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)。患有p16+/pRb-/细胞周期蛋白D1-/CDK4-或p16-/pRb+/细胞周期蛋白D1-/CDK4-肿瘤的患者表现出特别差的存活率。通过多变量生存分析，只有浸润深度和 TNM 分期可以被证明是独立的预测因素。结论：Rb 通路在绝大多数胃癌中被破坏。这项研究还确定了用于预后的特定免疫组织化学标记物谱。
Background and Objectives: The p 16(INK4a) (p16), cyclin D 1, 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 p26/Rb protein (pRb) expression and overexpression of cyclin D1/CDK4 were observed in 49%/40% and 37%/37% of gastric carcinomas, respectively. At least I of these abnormalities was found in 86% of the cases and a positive correlation was noted between p16 and pRb (P = 0.009). Cyclin D I (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 pl6+/pRb-/cyclin D1-/CDK4- or pl6-/pRb+/cyclin Dl-/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.