Abstract
ABSTRACT Introduction Aldehyde dehydrogenase 1 (ALDH1) has been identified as a marker of breast cancer (BC) stem cells. High expression of ALDH1 was shown to correlate with poor outcome of BC patients. Breast cancer susceptibility gene 1 (BRCA1), a well-known tumor suppressor gene frequently mutated or lost in hereditary BC, has been recently demonstrated to influence stem cells fate in in vitro studies. Nevertheless, its role in sporadic tumors is still poorly investigated. This study was designed to examine the clinical relevance of BRCA1 and ALDH1 in a cohort of sporadic BC patients. Materials and methods The study group included 163 patients with sporadic BC in stage I-III. Protein expression was examined by immunohistochemistry (IHC) on tissue-microarrays applying anti-human mouse monoclonal antibodies against BRCA1 (MS110, Calbiochem) and ALDH1 (Clone 44, BD Bioscience). The intensity of staining, the percentage of stained cells and staining localization were documented and compared to molecular and clinico-pathological parameters. Results ALDH1 was strongly positive in 14.7% of carcinomas whereas BRCA1 protein was expressed in 46.6% and lost in 54.4% of the examined cases. Inverse correlation between expression levels of BRCA1 and ALDH1 was found (p = 0.007). High ALDH1 expression was associated with high histological tumor grade (p = 0.03). Interestingly, co-expression of BRCA1 and ALDH1 correlated with shorter disease free survival (p = 0.03). Disease recurrence occurred in 33% of BRCA1 + /ALDH1+ cases (12/4) in comparison to 8% of BRCA1-/ALDH1+ cases (23/2). No correlation was found between BRCA1/ALDH1 phenotype and molecular subtypes of BC. Conclusions It was found that in sporadic BC co-expression of BRCA1 and ALDH1 is associated with poorer prognosis compared to BRCA1-/ALDH1+ phenotype. However, further studies would be needed to confirm these results. Disclosure All authors have declared no conflicts of interest.
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