胃癌和癌前病变中错配修复基因hMLH1的表达及意义

Expression of DNA mismatch repair gene hMLH1 and its significance in gastric cancer and premalignant lesions

目的：探讨DNA错配修复基因hMLH1在胃癌和癌前病变中的表达及临床意义．方法：应用免疫组织化学技术PV-6000二步法检测20例慢性浅表性胃炎、20例慢性萎缩性胃炎伴肠化生、8例胃腺瘤性息肉、58例胃癌患者癌组织及其癌旁组织的hMLH1基因蛋白表达．结果：hMLH1基因蛋白主要表达于黏膜上皮的细胞质内,少量表达于细胞核．在慢性浅表性胃炎上皮细胞和慢性萎缩性胃炎伴肠化生的阳性表达率(均为90%)明显高于胃腺瘤性息肉及胃癌旁组织上皮细胞的阳性表达率(分别为62．5%和62．1%),差别有统计学意义(X^2= 9．741,P=0．02)．hMLH1基因蛋白在胃癌细胞的表达率为72．41%,与前四者之间差别无统计学意义．在58例癌旁组织中,21例(36．2%)为慢性浅表性胃炎,37例(63．8%)为慢性萎缩性胃炎伴肠化生,二者hMLH1蛋白阳性表达率相近,但明显低于非胃癌患者慢性浅表性胃炎和慢性萎缩性胃炎伴肠化生的阳性表达率,差别具有统计学意义(X^2=9．885,P=0．02)．结论：hMLH1表达缺失可能是胃癌的早期分子事件,对hMLH1蛋白表达缺失的慢性胃炎患者进行随访、监测,可能有利于胃癌的早期诊断．

AIM： To investigate the expression of DNA mismatch repair gene hMLH1 and its clinical significances in gastric cancer and premalignant lesions. METHODS： Immunohistochemical technique was used to detect the expression of hMLH1 protein in 20 cases of chronic superficial gastritis, 20 cases of chronic atrophic gastritis complicated with intestinal metaplasia, 8 cases of adenomatous polyp, 58 cases of gastric cancer and the corresponding cancer-adjacent mucosa. RESULTS： The hMLH1 protein was expressed mostly in epithelial cytoplasm and a little in cell nucleus. The positive rate of hMLH1 expression in chronic superficial gastritis and chronic atrophic gastritis with intestinal metaplasia were all 90%, which were significantly higher （x^2 = 9.741, P = 0.02） than those in adenomatous polyp （62.5%） and the corresponding cancer-adjacent mucosa （62.1%）. The positive rate of hMLH1 expression was not significantly different between gastric cancer （72.4%） and the others （P 〉 0.05）. Of 58 cases of cancer-adjacent mucosa, 21 （36.2%） were with chronic superficial gastritis, and 37 （63.8%） with chronic atrophic gastritis and intestinal metaplasia. The positive rates of hMLH1 expression were similar between the 21 and 37 cases, but they were both markedly lower than those in the nonneoplastic mucosa （x^2=9.885, P =0.02）. CONCLUSION： Absence of hMLH1 expression may be one of the early molecular events in the carcinogenesis of gastric cancer. Timely visiting and monitoring chronic gastric patients with absence of hMLH1 protein expression may help to achieve early diagnosis of gastric cancer.