Expression intensity and localization of BAP1 in hereditary breast cancer correlates to TNM status
Docheva V.1, Kolben T.1, Kuhn C.1, Schochter F.2, Kolben T.M.1, Koelbl A.1, Gross E.1, Meindl A.1, Mahner S.1, Jeschke U.1,3, Ditsch N.3, Zeder-Göß C.1
1Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe - Ludwig-Maximilians-Universität München, München, Deutschland, 2Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm, Deutschland, 3Klinik für Frauenheilkunde und Geburtshilfe, Universität Augsburg, Augsburg, Deutschland
BRCA1- associated protein 1 (BAP1) interacts with BRCA1 in its tumour suppressor function. Recent studies described the role of BAP1 as an oncogene in breast carcinogenesis. Considering the interaction of BAP1 with BRCA1, we aimed to explore the expression and prognostic potential of BAP1 in BRCA1/2 mutated and BRCA1/2-negative tested cases.
We collected breast cancer tissue of 83 patients with an increased hereditary risk, who were treated in the university hospitals of Munich and Ulm between 1990 and 2003. The samples were analyzed for BAP1 expression by immunohistochemistry. The expression of BAP1 in the nucleus and cytoplasm was analyzed separately by using the IRS-score.
In a total of 36 of the patients Panel (TruRisk ®) results showed a mutation of either BRCA1 or BRCA2; 47 cases were BRCA1/2 negative. Analyzing the nuclear expression of BAP1 in BRCA1/2 mutation positive specimens, we found a higher BAP1- expression corresponding to higher pT-Status (p=0.005). In the BRCA1/2 wild-type specimens the cytoplasmatic BAP1 expression correlated with tumor size (p=0.016). Specimens with smaller tumours (pT1 and pT2) showed a moderate BAP1 expression, whereas pT3 and pT4-tumours had the lowest BAP1 expression. Additionally, for BRCA1/2 mutation negative specimens a negative correlation between BAP1- cytosol expression and axillary nodal status (p=0.036) could be demonstrated.
Although the exact function of BAP1 is still unclear, out study demonstrated a possible association between tumour size and affection of the axillary lymph nodes and the transit of BAP1 between cytosol and nucleus in relation to the BRCA1/2 mutation status.