[人胃腺癌中几种抑癌基因的启动子甲基化]

[Promoter methylation of several tumor suppressor genes in human gastric adenocarcinoma].

作者信息

Cai Jian-chun, Liu Di, Zhang Hai-ping, Zhong Shan, Xia Ning-shao

机构信息

Department of Tumor Surgery, Xiamen Cancer Center, Xiamen First Hospital Affiliated to Fujian Medical University, Xiamen 361003, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Apr 10;87(14):978-81.

PMID:17650424

Abstract

OBJECTIVE

To study the promoter methylation of several tumor suppressor genes in human gastric foveolar epithelia (GFE) of chronic gastritis, adjacent GFE of gastric adenocarcinoma (GAC) and GAC.

METHODS

Methylation specific PCR (MSP) technique was used to examine the promoter methylation of 4 tumor suppressor genes (E-cadherin, hMLH1, APC, and MGMT) in 106 paraffin-embedded specimens of GAC, including tumor tissues and adjacent GFE, and 16 paraffin-embedded specimens of GFE of chronic gastritis. Immunohistochemistry was used to detect the protein expression of E-cadherin (E-CD) in 46 out of the 106 cases of GAC.

RESULTS

The promoter methylation rates of tumor suppressor genes in the GAC tissue were 72.6% (77/106), significantly higher than that in the adjacent GFE (44.3%, 47/106) and the GFE of chronic gastritis (12.5%, 2/16, P < 0.01). The promote methylation rate of tumor suppressor genes in the GAC Laurén diffuse type was 80.6% (50/62), significantly higher than that of the GAC of intestinal type (61.4%, 27/44, P < 0.01). The rates of promoter methylation was significantly associated with depth of penetration, pTNM staging and degree of differentiation in GAC (all P < 0.05), but was no significantly associated with age, gender, Ming's classification and local lymph node metastasis (all P > 0.05). The rate of loss of E-CD protein expression or heterogeneously reduction of E-CD protein expression in the specimens of GAC with promoter methylation was 90.9% (20/22), significantly higher than that in the specimens of GAC without promoter methylation (9/24, 37.5%, P < 0.01).

CONCLUSION

Promoter methylation of above tumor suppressor genes is seldom found in the GFE of chronic gastritis, frequently found in the adjacent GFE of GAC, but very commonly in GAC. Promoter methylation may be an early event in the carcinogenesis of GAC. E-CD gene promoter methylation is closely related to loss or heterogeneously reduction of E-CD protein expression.

摘要

目的

研究慢性胃炎患者胃小凹上皮（GFE）、胃腺癌（GAC）癌旁GFE及GAC中几种抑癌基因的启动子甲基化情况。

方法

采用甲基化特异性PCR（MSP）技术检测106例GAC石蜡包埋标本（包括肿瘤组织及癌旁GFE）及16例慢性胃炎GFE石蜡包埋标本中4种抑癌基因（E-钙黏蛋白、hMLH1、APC和MGMT）的启动子甲基化情况。采用免疫组织化学法检测106例GAC中46例的E-钙黏蛋白（E-CD）蛋白表达。

结果

GAC组织中抑癌基因启动子甲基化率为72.6%（77/106），显著高于癌旁GFE（44.3%，47/106）及慢性胃炎GFE（12.5%，2/16，P<0.01）。GAC劳伦弥漫型中抑癌基因启动子甲基化率为80.6%（50/62），显著高于肠型GAC（61.4%，27/44，P<0.01）。GAC中启动子甲基化率与浸润深度、pTNM分期及分化程度显著相关（均P<0.05），但与年龄、性别、明氏分类及局部淋巴结转移均无显著相关性（均P>0.05）。启动子甲基化的GAC标本中E-CD蛋白表达缺失或异质性降低率为90.9%（20/22），显著高于无启动子甲基化的GAC标本（9/24，37.5%，P<0.01）。