The Expression Of Brca1 In Basal-like Breast Cancer And Its Relationship With Id4

Background and objectives Gene-expression profiling has revealed several molecular subtypes of breast cancer, which differ in their pathobiology and clinical outcomes. Basal-like tumors are a newly recognized subtype of breast cancer, which express genes that are characteristic of basal epithelial cells, such as the basal cytokeratins, and are associated with poor relapse-free and overall survival. At present, most information about basal-like breast cancer is based on the studies of western populations,little is known about that of Chinese population. Pathogenesis of basal-like tumors is not clear. Breast cancers arising in carriers of germline BRCA1 mutations are predominately of basal-like type, suggesting that BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers. In the current study, we categorized a large group of invasive breast cancers by tissue microarray and immunohistochemistry, and described the distribution and clinicopathologic of basal-like breast cancer in Chinese population.Then,we detected the expression of BRCA1 protein and BRCA1mRNA in basal-like breast cancer ,and analysed its relationship with ID4 and molecular markers,exploring.the role of BRCA1and BRCA1 pathway in the basal-like breast cancer.Methods1. 1452 invasive breast cancer was collected to make tissue microarray.2. Immunohistoehemistry was used to detect the expression of ER,HER2,CK5/6,EGFR. Based on the results, the cases were categorized according to Nielson criteria. Then we described the distribution and clinicopathologic of basal-like breast cancer.3. Immunohistoehemistry was used to detect the expression of BRCA1 and ID4 in the breast carcinoma molecular subtypes.4. In situ hybridization was used to detect the BRCA1mRNA in the breast carcinoma molecular subtypes.Results1. Basal-like breast cancers constituted 17.0% of 1311 invasive breast cancers, showed significantly bigger size, more frequent recurrence, infrequent node metastasis and higher grade.2. Positive expression ratio of BRCA1 protein in basal-like breast cancer was 63.0%(136/216), lower than luminal A subtype(P<0.001)and luminal B subtype(P<0.001),however, no significant difference was found between basal-like subtype and other ER negative breast cancer subtype. Positive expression ratio of BRCA1mRNA in basal-like breast cancer was 30.0%, lower than other breast carcinoma molecular subtypes.3. Positive expression ratio of ID4 protein in basal-like brast cancer was 64.6%(117/181), higher than luminal A subtype(P<0.001)and luminal B subtype(P<0.01),however, no significant difference was found between basal-like subtype and other ER negative breast cancer subtype. ID4 and ER protein levels were inversely correlated.(r=-0.202, P<0.001).4. A positive association was observed between the protein expression of BRCA1 and ER(r=0.254, P<0.001),and an inverse correlation was observed between the protein level of expression of BRCA1 and ID4(r=-0.261,P<0.001). No association was found in the protein level of expression of BRCA1,CK5/6 and EGFR.Conclusions1.Basal-like breast cancers have distinct clinicopathologic features, and its prevalence in Chinese population is similar to that of western populations.2.Down regulation of BRCA1 protein and BRCA1mRNA in the basal-like breast cancer, suggesting BRCA1 dysfunction may play a role in the pathogenesis of sporadic basal-like cancers .3. ID4 protein was overexpressioned in the basal-like breast caner, the levels of expression of ID4 were inversely correlated with BRCA1 levels,。Overexpression of ID4 in basal-like cancers may, therefore, provide an explanation for BRCA1 down regulation in this subtype.4. The levels of expression of ER were positive correlated with BRCA1 and inversely correlated with ID4 levels, the participation of ER in the molecular events that maybe regulate BRCA1and ID4 expression, or vice versa.