The Expression of BRCA1-Associated Protein 1 (BAP1) in Dermal Melanoma
Akeesha A Shah, Louis B Brill, Mark J Mentrikoski, Craig Slingluff, Mark R Wick, Edward B Stelow. University of Virginia, Charlottesville
Background: BRCA1-Associated Protein 1 (BAP1) is a nuclear localized enzyme that belongs to the family of ubiquitin carboxy-terminal hydrolases. It is present on chromosome 3p21 in an area that has been shown to undergo both germline and somatic mutations. Recently, a number of kindreds known to develop both mesotheliomas and uveal melanomas have been shown to harbor germline mutations in BAP1 as have sporadic mesotheliomas. While somatic mutations of BAP1 have been demonstrated in 5% of skin and mucosal melanomas, a detailed study of protein expression has not been conducted. Here, we show our results using BAP1 immunohistochemistry with a series of dermal melanomas.
Design: A tissue microarray was constructed using 42 metastatic melanomas (37 from dermal tumors, 1 from a mucosal tumor and 4 from unknown primary sites) from 22 men and 20 women with a mean age of 60 years (range 26-88). Immunohistochemistry was performed using the BAP1 antibody (Santa Cruz). Nuclear staining was scored as either positive or negative (complete absence of staining). Cytoplasmic staining intensity was assessed on a scale of 0 (no staining) to 3+ (diffuse strong positivity).
Results: Loss of nuclear staining was seen in 15 cases (36%). Cytoplasmic staining was intense in 33% of cases, moderate in 29% of cases and weak in 38% of cases. The figure shows intact nuclear staining (right) and loss of nuclear staining (left) with weak cytoplasmic staining.
Conclusions: In spite of the fact that somatic mutations of BAP1 have only been observed in 5% non-uveal melanomas, 35% of our metastatic melanomas showed a loss of nuclear localization of the protein. This suggests that other factors may play some role in rendering BAP1 under-expressed or non-functional in dermal melanomas.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 118, Wednesday Afternoon