BAP1 Expression in Melanoma of the Skin
Rajmohan Murali, James Wilmott, Valerie Jakrot, Hikmat Al-Ahmadie, Thomas Wiesner, Stanley McCarthy, John Thompson, Richard Scolyer. Memorial Sloan-Kettering Cancer Center, New York, NY; Melanoma Institute Australia, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia
Background: BAP1 is a tumor suppressor gene that was initially thought to function in the BRCA1 growth control pathway, but has more recently been shown to play a role in chromatin modification and transcriptional regulation. Somatic mutation and/or loss of BAP1 is seen in a variety of tumors, and is associated with poor prognosis in patients with uveal melanoma. In this study, we evaluated immunohistochemical (IHC) expression of BAP1 in cutaneous melanomas, and investigated associations of BAP1 expression with clinico-pathologic parameters and survival.
Design: BAP1 IHC was performed in tissue microarrays (TMAs) of selected primary cutaneous melanomas from patients treated at Melanoma Institute Australia between 1992 and 2009. The tumors in the TMAs had been selected to represent a range of thick melanomas of various histologic subtypes. We analyzed associations of BAP1 expression with pathologic and clinical parameters, and with disease-free and melanoma-specific survival.
Results: In 158 melanoma patients [median age 72.2 years; 64 females, 94 males], stages at diagnosis were: I (n=15, 9.5%), II (n=90, 57.0%), III (n=43, 27.2%), IV (n=3, 1.9%), and unknown (n=7, 4.4%). Median Breslow thickness was 4.80mm (range 0.80-21.70mm), median mitotic rate was 6/mm2 (range 0-50/mm2), and ulceration was present in 73 (46.8%) tumors. BAP1 expression was absent in 9 (5.6%) tumors. Desmoplastic melanomas were more frequently (21.7%) BAP1-negative than non-desmoplastic melanomas (3%; p<0.0001). There were no statistically significant associations between loss of BAP1 expression and other clinico-pathologic parameters. Higher stage at diagnosis, increasing mitotic rate, presence of LVI and absence of BAP1 expression were independently associated with poorer disease-free survival and melanoma-specific survival.
Conclusions: Loss of BAP1 expression was seen in ∼5% of melanomas overall, but it was associated with a disproportionately higher percentage of desmoplastic melanomas than non-desmoplastic melanomas. BAP1 loss was independently associated with poorer survival. Further, studies are required to explore the spectrum of BAP1 expression in desmoplastic melanomas, and to validate the prognostic significance of loss of expression of BAP1.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 43, Tuesday Morning