乳腺癌组织中BRCA1的蛋白表达与乳腺癌的相关性分析研究

Correlation of the BRCA1 protein expression and breast cancer

目的乳腺癌易患基因1(breast cancer susceptibility gene 1,BRCA1)变异及其蛋白产物功能的改变与乳腺癌的发生密切相关,对调节细胞周期,修复DNA损伤,诱导细胞凋亡起重要作用。对BRCA1功能及蛋白产物的研究有利于阐明肿瘤的发生机制。文中分析BRCA1蛋白表达与乳腺癌临床分期组织学分级及临床病理参数的相关性。方法 80例乳腺癌手术标本的存档蜡块,用Envision免疫组化法检测BRCA1蛋白。分析BRCA1的表达和患者的年龄、肿物大小、淋巴结转移情况及雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、Her-2、p53表达的关系。结果经多样本χ2检验,无淋巴结转移与淋巴结转移组之间的BRCA1蛋白表达有显著性差异(P=0.035),转移1～3个淋巴结、4～9个淋巴结、10个以上淋巴结3组之间的BRCA1蛋白表达有显著性差异(P=0.023)。BRCA1的表达与淋巴结转移呈正相关(r=0.414,P<0.05)。BRCA1蛋白在ER阴性组的表达率高于ER阳性组(P=0.002),在PR阴性组的表达高于PR阳性组,在HER-2阴性组的表达高于HER-2阳性组,且均有显著性差异(P<0.05)。BRCA1蛋白在p53阳性组的表达高于p53阴性组,有显著性差异(P<0.05)。BRCA1蛋白在≤45岁年龄组与>45岁年龄组的表达差异无统计学意义(P=0.629)。BRCA1蛋白在不同肿瘤大小组间的表达差异无统计学意义(P=0.953)。结论 BRCA1的表达与ER、PR、HER-2呈负相关,与组织学分级及p53表达呈正相关,与淋巴结转移呈正相关,与肿物大小及年龄无关。

Objective Breast cancer susceptibility gene 1(BRCA1) mutation and the function variation of its corresponding protein are closely related to the occurrence of breast cancer,and play an important role in the regulation of cell cycles,repair of DNA damage and induction of cell-apoptosis.Researches on the functions of BRCA1 and its corresponding protein may offer an insight into tumor pathogenesis.This study was to investigate the correlation of the expression of the BRCA1 protein with the clinical stages,histological grades and clinicopathologic parameters of breast cancer.Methods We detected the expression of the BRCA1 protein in 80 cases of breast cancer using the envision immunohistochemical method,and analyzed the relationship of BRCA1 expression with the clinicopathologic parameters of the cases,including age of onset,tumor size,axillary nodal status,and the expressions of the estrogen receptor(ER),progesterone receptor(PR),Her-2 and p53.Results There were significant differences in the expression of the BRCA1 protein between the group of no lymph node metastasis and that of lymph node metastasis(P=0.035),as well as among those with 1-3 lymph nodes metastasis,4-9 lymph nodes metastasis and more than 10 lymph nodes metastasis(P=0.023).Spearman correlation analysis showed that BRCA1 expression was positively related to lymph node metastasis(r=0.414,P<0.05).A significantly higher expression of BRCA1 was found in the ER-,PR-,HER-2-and p53+ groups than in the ER+,PR+,HER-2+ and p53-groups(P<0.05).There were no significant differences in the BRCA1 expression between the age groups of ≤45 and >45 years(P=0.629),nor among different tumor sizes(P=0.953).Conclusion The expression of the BRCA1 protein is correlated negatively with ER,PR and HER-2,positively with histologic grades,p53 expression and lymph node metastasis,but not with the tumor size and patients′ age.