乳腺癌微卫星不稳定性及其与临床病理关系的研究

目的：探讨乳腺癌的微卫星不稳定性及其与乳腺癌临床病理的关系,寻找更有效的判断乳腺癌预后的分子标志,为乳腺癌的发生及预后判断提供理论依据。方法：提取18例正常乳腺组织,39例乳腺良性肿瘤组织和78例乳腺癌组织的DNA,参考文献选取D2S443、D11S988、D21S1436、D3S1766、D2S2739这5个微卫星位点,在基因库中查出相应的引物序列,PCR扩增位点的DNA,然后用12%聚丙烯酰胺凝胶电泳,银染显色后进行微卫星不稳定性的分析。用免疫组化S-P法检测HER2、ER、PR在乳腺癌中的表达情况。结果：18例正常乳腺组织未见微卫星不稳定（microsatellite instability,MSI）发生,39例乳腺良性肿物组织中有5例至少1个位点发生MSI,MSI的发生率为12.82%（5/39）。78例乳腺癌中有35例至少1个位点出现MSI,MSI的发生率为44.87%（35/78）,3组比较差异均有统计学意义（χ2=^20.365,P=0.000）,MSI的发生率与乳腺癌的腋窝淋巴结转移、临床分期及HER2表达有相关性（分别为P=0.018,P=0.04,P=0.039）。结论：乳腺癌中普遍存在着MSI,并且MSI更多发生在有腋窝淋巴结转移、HER2表达及临床分期晚的病例中,提示预后较差的乳腺癌病例中MSI的发生率更高,MSI可能是判断乳腺癌临床分期的一个分子标志,有助于对乳腺癌的预后评估。

STUDY ON MICROSATELLITE INSTABILITY IN BREAST CANCER

Objective：To investigate the mechanism and effects of microsatellite instability（MSI） in breast cancer.Methods：Seventy-eight samples of breast cancers,39 samples of benign tumor of breast and 18 samples of normal control were studied.DNA was extracted by DNA extracted kit.Five microsatellite situs were choosed according to the literature and findout their sequences in gene bank.The MSI was analyzed by PCR-single strand strand conformation polymorphism（SSCP）.Results：MSI isn＇t presented in normal tisssues,5 of 39 breast benign tumor tissues can found MSI in at least one microsatellite situs,the rate of MSI was 12.82%.Thirty-five of 78 breast cancer tissues can found MSI in at least one microsatellite situs,the rate of MSI was 44.87%.There was statistical difference in these three groups（χ^2=20.365,P〈0.05）.Significant correlation was observed between the MSI and these axillary nodes metabasis,clinical stage and the expression of HER2 gene in breast cancer.Conclusion：MSI is widespread in breast cancer,it is more easily observed in the tissues with later clinical stage,metabasis of axillary nodes and highly expression of HER2 gene.These results indicate that patients with MSI maybe poor prognostic.MSI can be a genetic marker for clinical stage of breast cancer,it helps to predicted prognostic of breast cancer.