HNPCC大肠腺瘤及癌组织微卫星不稳定与TGFβRII表达的关系

The relationship between microsatellite instability and the expression of TGFβRII in HNPCC adenocarcinomas and adenomas

目的观察遗传性非息肉病性大肠癌(HNPCC)和大肠腺瘤癌组织中TGFβRII、错配修复基因(hMLH1、hMSH2、hMSH6)蛋白表达和微卫星不稳定(MSI)的关系。方法以来源于33个HNPCC家系的大肠腺瘤28例和大肠腺癌14例为观察对象,以32例散发性大肠腺瘤和24例散发性大肠癌作为对照。采用免疫组织化学技术,检测大肠腺瘤及大肠腺癌组织中TGFβRII、hMLH1、hMSH2、hMSH6蛋白表达。从活检组织中提取DNA,选择BAT-25、BAT-26、D2S123、D5S346、D17S250五个微卫星位点行荧光标记聚合酶链反应(PCR),以GeneMapper软件分析PCR产物。通过与正常黏膜微卫星序列PCR片断长度进行比较,判定腺瘤和癌组织的MSI情况。结果64.29%的HNPCC大肠腺瘤和71.43%的HNPCC大肠癌表现为MSI-H,明显高于散发性大肠腺瘤9.38%和散发性大肠癌12.5%。分别有67.86%的HNPCC大肠腺瘤和71.43%的HNPCC大肠癌表现为MMR蛋白表达缺失,明显高于散发性大肠腺瘤3.13%和散发性大肠癌12.5%。分别有57.14%的HNPCC大肠腺瘤和78.57%的HNPCC大肠癌表现为TGFβRII低表达,明显高于散发性大肠腺瘤9.38%和散发性大肠癌41.67%。在MSI-H的HNPCC大肠腺瘤中,TGFβRII低表达者占77.78%,MSI-H的HNPCC大肠癌中90%出现TGFβRII的低表达。MSI-H的散发性大肠腺瘤中TGFβRII的低表达率为66.67%,MSI-H的散发性大肠癌TGFβRII的低表达率为100%。结论大部分HNPCC大肠腺瘤和大肠癌出现MSI-H,大部分MSI-H大肠腺瘤和大肠癌表现为TGFβRII低表达。MSI、MMR、TGFβRII的检测对腺瘤癌变风险的估计具有重要意义。

Objective To investigate the relationship between microsatellite instability （MSI） and the expression of transforming growth factor β receptor II （TGFβRRII）, mismatch repaire （MMR） proteins in Hereditary Non-polyposis Colorectal Cancer（HNPCC）. Methods Twenty-eight adenomas, 14 adenocarcinomas from 33 HNPCC families were collected. Thirty-two sporadic colorectal adenomas and 24 sporadic colorectal adenocarcinomas served as controls. The expressions of TGFβRRII and MMR proteins were examined by immunohistochemistry（IHC）. Genomic DNA was extracted from biopsy tissues. MSI were analyzed by using fluorescent primers PCR with BAT-25, BAT-26, D2S123, D5S346, D17S250 locus. Results The incidence of MSI-H was 64.29% in HNPCC adenomas and 71.43% in HNPCC adeno- carcinomas,and it was higher than that in sporadic colorectal adenomasg. 38% and sporadic adenocarcinomas 12.5%. The rates of MMR protein expression absence were 67.86% and 71.43% in HNPCC adenomas and adenocarcinomas, and it was higher than that in sporadic adenomas 3. 13% and sporadic adenocarcinomas 12.5%. The TGF13RII low-ex- pression rates were 57. 14% and 78.57% in HNPCC adenomas and adenocarcinomas,and it was higher than that in adenomas 9.38% and sporadic adenocarcinomas 41.67%. The TGF13RII low-expression rate was 77.78% in HNPCC MSIH colorectal adenomas, and it was 90% in HNPCC MSI-H colorectal adenocarcinomas. There was also a high incidence of TGFβRRII low-expression in sporadic colorectal adneomas 66.67% and sporadic adenocarcinomas 100%. Conclusion Most HNPCC adenomas and adenocarcinomas were classified as MSI-H. TGFβRRII low-expression occurred in most MSI-H adenomas and adenocarcinomas. In order to investigate cancer risk, it is important to detecte MMR protein,TGFβRRII expression and MSI in colorectal adenomas.