Immunohistochemical Detection of BRCA-1 and BRCA-2 Expression in Human Breast and Ovarian Tumors

Abstract

Breast cancer susceptibility proteins 1 and 2 (BRCA-1 and BRCA-2) are two key tumor suppressor genes that play important roles in tumorigenesis. Functional loss or reduction of BRCA-1 and/or BRCA-2 protein expression often leads to poor clinical outcomes in breast and ovarian cancer patients. To explore the utility of BRCA-1 and -2 as potential predictive biomarkers for targeted therapeutic approaches, we optimized and used an immunohistochemistry procedure to determine the expression profiles of BRCA-1 and BRCA-2 proteins on a large number of human breast and ovarian tumors and corresponding normal tissues. We found the expression of BRCA-1 and BRCA-2 proteins was down-regulated in breast and ovarian tumors when compared with corresponding normal tissues. BRCA-1 expression was detected in 100% of normal breast tissues whereas it was expressed in 91% and 71% of primary and metastatic tumors, respectively. Furthermore, the expression levels of BRCA-1 were lower in the majority of primary and metastatic tumors when compared with normal breast. In comparison with 100% expression in normal breast tissues, BRCA-2 protein was detected in 73% and 67% of primary and metastatic tumors, respectively. The expression levels of BRCA-2 in the majority of primary and metastatic tumors were also lower than in normal breast tissues. BRCA-1 expression was detected in 100% of normal ovary tissues as well as primary ovarian tumors, whereas 16 of 17 lymph node metastatic ovarian tumors had detectable BRCA-1 expression. Expression of BRCA-2 was detectable in 100% of normal ovary tissues whereas in only 50% and 61% of primary and metastatic tumors, respectively. Expression levels of BRCA-1 and BRCA-2 proteins were also lower in the majority of primary and metastatic ovarian tumors when compared with normal ovary tissues. In conclusion, we found that expression of BRCA-1 and -2 proteins were significantly down-regulated in breast and ovarian tumors, especially in metastatic tumors. The usefulness of these markers as predictive biomarkers for targeted therapy will be discussed. (The J Histotechnol 32(4):202–203, 2009)