子宫内膜癌中人类乳腺癌易感基因1微卫星不稳定性及其与临床病理的关系

BRCA1 microsatellite instability in endometrial carcinoma and its relationship with clinical pathology

目的:研究人类乳腺癌易感基因1(BRCA1)在子宫内膜癌中微卫星不稳定性(MSI)发生情况及其与临床病理特征的关系。方法:采用聚合酶链反应-单链构象多态性分析(PCR-SSCP)法和DNA序列分析法,分别对77例子宫内膜组织BRCA1基因2个位点进行MSI测定。结果:子宫内膜癌、子宫内膜不典型增生、正常子宫内膜组MSI阳性率分别为34.69%(17/49)、10%(2/20)、7.14%(2/28),差异有统计学意义(χ2=11.208,P=0.004)。BRCA1 MSI阳性率与病理分级和临床分期有关,而与肌层浸润深度、淋巴结转移、组织病理类型无关。BRCA1 MSI与BRCA1蛋白表达水平呈负相关(P=0.000)。结论:BRCA1基因MSI可能是子宫内膜癌的发生发展以及BRCA1蛋白表达减少的原因之一,与子宫内膜癌病理分级和临床分期有关。

Objective To study the occurrence of BRCA1 MSI in endometrial cancer and its relationship with clinic pathologic features; to explore the correlation between MSI and protein expression in BRCA1 gene. Methods Application of PCR-SSCP and DNA sequence analysis method was used to study D17S579 and D17S1349 in 49 sporadic endometrial cancer tissues, 20 cases with endometrial atypical hyperplasia and 28 cases with normal endometrial tissues. Results In the total samples of D17S579 and D17S1349, the three groups were significantly different： 34.69%（17/49） in the endometrial cancer group, 10% （2/20） in the endometrial atypical hyperplasia group and 7.14%（2/28） in the normal endometrium group （x^2 = 11.208, P = 0.004）. BRCA1 MSI positive rate related to the pathology grade and clinical stage, but no relationship was found in muscular infiltration depth, lymph node metastasis and histopathology types. In the endometrial cancer group, BRCA1 MSI positive rate and BRCA1 protein expression were in moderate correlated negatively （r = -0.779, P = 0.000）. Conclusion BRCA1 MSI might play a role in the development of endometrial cancer, and low expression of BRCA1 protein. BRCA1 MSI might be associated with pathology grade and clinical stages in EC.