老年人胃癌肿瘤抑制基因启动子区甲基化状态

Tumor Suppressor Genes Promoter Methylation in Elderly Patients with Gastric Carcinoma

目的分析老年人胃癌组织及其癌旁小凹上皮和慢性胃炎小凹上皮中肿瘤抑制基因启动子区甲基化状态。方法采用甲基化特异性聚合酶链反应(MSP)方法,检测51例老年人胃癌及其癌旁小凹上皮和15例慢性胃炎小凹上皮石蜡标本中E钙黏素(E-CD)、错配修复酶hMLH1、APC和6-氧-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子区甲基化状态。结果在胃癌组织及其癌旁小凹上皮和慢性胃炎小凹上皮中,基因总的甲基化率分别为70.6%(36/51例)、47.0%(24/51例)和6.6%(1/15例),三者之间差别有统计学意义(P<0.01)。Lauren弥漫型、Ming浸润型、低分化和未分化、Ⅲ期和Ⅳ期、T3和T4以及有淋巴结转移胃癌的甲基化率分别高于Lauren肠型、Ming膨胀型、高和中分化、Ⅰ期和Ⅱ期、T1和T2以及无淋巴结转移胃癌的甲基化率(均P<0.05)。结论E-CD、hMLH1、APC和MGMT基因启动子区甲基化在慢性胃炎小凹上皮中少见,在癌旁小凹上皮中频繁出现,在胃癌组织中普遍存在,提示甲基化可能是胃癌发生的早期事件。

Objective To study the promoter methylation status of several tumor suppressor genes in human gastric pit epithelia（GE） of chronic gastritis, adjacent gastric adenocarcinoma（GC） and GC. 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 paraffin-embedded specimens of 51 cases GC, including tumor tissues and adjacent GE, and 15 GE of chronic gastritis. Results The promoter methylation rates of tumor suppressor genes in the GC tissue were 70. 6% （36/51）, significantly higher than that in the adjacent GE（47. 0%, 24/51） and the GE of chronic gastritis（10. 0%, 1/10, P〈0.01）. The rates of promoter methylation was significantly associated with the Laur6n classification, Ming classification, degree of differentiation, pTNM staging, depth of penetration and local lymph node metastases in GC（all P〈0.05）, respectively. Conclusion The tumor suppressor genes promoter methylation were common and early event in carcinogenesis of gastric carcinoma in elderly patients.