BRCA1 Protein Expression Level and CD44+ Phenotype in Breast Cancer Patients

CD44+/CD24-/low breast cancer cells have tumour-initiating properties with stem cell-like features. Breast cancer gene 1 (BRCA1) is a tumour suppressor gene that plays a crucial role in DNA repair and maintenance of chromosome stability. The clinicopathological features of breast cancer in BRCA1 mutation carriers suggest that BRCA1 may function as a stem-cell regulator. In the present experimental study we examined the expression and localization of the BRCA1 protein and investigated the prognostic value as well as its relationship with the putative cancer stem cell (CSC) marker (CD44) in 156 tumour samples from a well-characterized series of unselected breast carcinomas using immunohistochemistry. Statistical analysis of the data was performed using SPSS software version 16 (Chicago, IL, USA). In breast tumours, the loss of nuclear expression was detected in 23 cases (15%), whereas cytoplasmic expression of BRCA1 was observed in 133 breast carcinomas (85%). Altered BRCA1 expression was significantly associated with high grade and poor prognosis breast tumours (p=0.006). We further established an inverse significant correlation between BRCA1 expression levels and CD44+ cancer cell phenotype (p=0.02) Loss of BRCA1 expression is a marker of tumour aggressiveness and correlates with CD44+ tumour cell phenotype. Taken together, the present study supports the idea that the loss of BRCA1 results in persistent errors in DNA replication in breast stem cells and provides targets for additional carcinogenic events.