胃癌中的细胞周期调控因子、APC/β-连环蛋白、NF-κB 和 Epstein-Barr 病毒。

Cell cycle regulators, APC/beta-catenin, NF-kappaB and Epstein-Barr virus in gastric carcinomas.

机构信息

Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea.

出版信息

Pathology. 2010 Jan;42(1):58-65. doi: 10.3109/00313020903356392.

DOI:10.3109/00313020903356392

PMID:20025482

Abstract

AIMS

To evaluate the clinicopathological value of cell cycle regulators, the Wnt pathway, the NF-betaB pathway and Epstein-Barr virus (EBV) and to assess their relationships in gastric carcinoma.

METHODS

We investigated cell cycle regulators (p53, p21, Rb), APC, beta-catenin and NF-kappaB using immunohistochemistry and EBV using in situ hybridisation for EBV encoded small RNAs in 117 cases of gastric carcinoma.

RESULTS

p53 overexpression was more frequently observed in advanced gastric carcinoma and lymph node metastasis than in early carcinoma or in the absence of metastasis (p < 0.05). p21 loss was positively correlated with APC loss, but inversely correlated with beta-catenin nuclear accumulation and NF-kappaB positivity (p < 0.05). EBV positive gastric carcinomas were located in the upper third of the stomach, and more were of the diffuse or mixed types than the EBV negative group (p < 0.05). EBV infection was positively correlated with p21 loss and APC loss and inversely correlated with beta-catenin alteration (p < 0.05). In multivariate analysis, patient age, TNM stage and p53 were independent prognostic factors for gastric carcinoma.

CONCLUSIONS

p53 status is a prognostic marker for gastric carcinoma. p21, APC, beta-catenin and NF-kappaB may be functionally interrelated in gastric carcinogenesis. Loss of p21 and APC may be involved in the carcinogenesis of EBV positive gastric carcinomas.

摘要

目的

评估细胞周期调控因子、Wnt 通路、NF-κB 通路和 Epstein-Barr 病毒（EBV）的临床病理价值，并探讨它们在胃癌中的关系。

方法

我们应用免疫组织化学方法检测了 117 例胃癌组织中细胞周期调控因子（p53、p21、Rb）、APC、β-连环蛋白和 NF-κB，应用原位杂交方法检测了 EBV 编码的小 RNA。

结果

p53 过度表达在晚期胃癌和淋巴结转移中比早期癌或无转移时更为常见（p<0.05）。p21 缺失与 APC 缺失呈正相关，与β-连环蛋白核积聚和 NF-κB 阳性呈负相关（p<0.05）。EBV 阳性胃癌位于胃上部，弥漫型或混合型多于 EBV 阴性组（p<0.05）。EBV 感染与 p21 缺失和 APC 缺失呈正相关，与β-连环蛋白改变呈负相关（p<0.05）。多因素分析显示，患者年龄、TNM 分期和 p53 是胃癌的独立预后因素。