Expression intensity and localization of BAP1 in hereditary breast cancer is associated with poor prognosis

Aim BRCA1- associated protein 1 (BAP1) plays a critical role in the tumour suppressor function of BRCA1. Recent studies discussed the role of BAP1 as an oncogene by stimulating metastasis and proliferation in breast carcinogenesis. Given the interaction of BAP1 with BRCA1, we aimed to explore the expression and prognostic potential of BAP1 in BRCA1/2 mutated and Panel-negative tested cases.

Materials and methods We collected breast cancer tissue of 90 patients with an increased hereditary risk for this tumour entity, 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 semiquantitative IRS-score.

Results In a total of 37 of the patients Panel (TruRisk ^®) results showed a pathologic mutation of either BRCA1 or BRCA2 and 53 cases were BRCA1/2 negative. Analyzing the nuclear expression of BAP1 in BRCA1/2 mutation positive specimens, we identified a negative correlation between BAP1- expression and long term survival (p = 0.004). Patients with BRCA1/2 mutation negativity and cytoplasmatic BAP1 expression showed a poor survival rate (p = 0.039). Overall, BAP1 expression was associated with poor survival.

Conclusion Although the exact function of BAP1 remains ambiguous, our study showed that the transit of this protein between cytoplasm and nucleus shows possible association with survival related to the BRCA1/2 status. Studies exploring the function of BAP1 as an oncogene in hereditary breast cancer are lacking.

Publication History

Article published online:
07 October 2020