The Expression Of BRCA1 Protein In Sporadic Breast Cancer And Its Clinical Significance

[Objective]: BRCAl,the first breast cancer susceptibility gene, was localized to chromosome 17Q by linkage analysis of multiple families affected by early-onset breast and ovarian cancer in 1990.Although mutations in BRCA1 are responsible for nearly 80% of familial breast cancer, its involvement in the majority of breast cancers, which are sporadic and not familial, has not been demonstrated clearly, Decreased mRNA levels or aberrant subcellular location of BRCA1 have been identified in sporadic breast cancer tissues. Our research is to investigate the expression of BRCA1 protein in large series of sporadic breast cancer and its correlation with other pathological parameters as well as clinical significance in sporadic breast cancer.[Methods]: The BRCA1 expression in normal breast tissue(n=31), in benign tumor of breast and in sporadic cases of breast carcinoma (n=132) was determined by using immunohistochemistry. BRCA1 expression was correlated with other molecular biological parameters including P53, ER, C-erbB-2, Ki67 and some prognostic parameters including age, histological grade, tumor size, axillary lymph node status and prognosis.[Results]: (1) BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma. In all 132 breast cancer cases, 96(72.7%) have BRCA1 expression exclusively in nuclear,6(4.54%) have both nuclear and cytoplasmic expression and 30(22.7%) have absent expression of BRCAl.(2) Absence of BRCAl expression in nuclei correlated well with high histological grade(P<0.05), poor prognosis(P<0.01), ER-negative, P53-positive and high Ki67 expression. Tumors.(3) there was no significant relationship between BRCAl expression and age, tumor size, axillary lymph node metastasis, histological types, and C-erbB-2 expression.[Conclusion]: BRCAl nuclear expression could be considered to represent the normal or physiological phenotype. Aberrant BRCAl expression in breasr carcinoma tissue and its correlation with other poor prognostic parameters suggest that BRCAl expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma. Altered BRCAl phenotype may therefore provide an additional prognostic parameter for breast cancer.