Abstract 3591: Triple negative (c-KIT, BRAF, NRAS) acral lentiginous melanoma in Hawaii: Molecular profiling in a multi-ethnic population

Abstract

Abstract Background: Acral lentiginous melanoma (ALM) is the least common subtype among patients with melanoma. There is a higher preponderance in the minority population. A different pathogenesis has been proposed for ALM. Previous studies have profiled the importance of c-KIT, BRAF and NRAS mutations in melanoma treatment and prognosis. However, characterization of these somatic mutations in a specific non-Caucasian ALM population has not been reported. The Pacific Basin provides a unique opportunity to study diseases in diverse ethnic groups, including Pacific Islanders and Filipinos. We sought to determine the frequency of a “triple negative” genotype in our multi-ethnic cohort. Methods: IRB approval was obtained for this molecular analysis. From 1999 to 2011, 12 non-Caucasian patients (8-Filipino, 3-Pacific Islander and 1-Vietnamese) histologically confirmed to have ALM were evaluated at a tertiary institution. Data including age, gender, tumor location, Breslow thickness, Clark level, ulceration, regression, and mitoses per mm squared were compiled. Direct sequencing (c-KIT [Exons 8,9,11,13,17,18], NRAS [Exons 2,3]) and real-time PCR (BRAF [Exon 15]) was performed on formalin-fixed/ paraffin-embedded archived biospecimens (primary lesions). Results: Our findings demonstrated that 7/12 (58%) patients exhibited the “triple negative” genotype. Mutually exclusive somatic mutations (4 c-KIT and 1 BRAF) were identified in the remaining 5/12 (42%) patients. Those in the “triple negative” group trended toward a deeper Breslow thickness, when compared to those with a mutation (depth 4.73 mm vs. 3.07 mm). Demographics of the entire non-Caucasian cohort included a mean age of 72.0 years old (range 52-87) and male gender 6/12 (50%). Tumor location principally involved the foot 10/12 (83%); mean Breslow thickness was 4.04 mm (range 2.20-7.75), Clark IV or higher 11/12 (92%), ulceration 8/12 (67%), regression 12/12 (100%), and mean mitoses per mm squared was 5.71 (range 0-30). Conclusions: Non-Caucasian patients with ALM were found to have a high prevalence of the “triple negative” genotype. Those within that group appeared to have thicker tumors. Nearly half of our cohort had thick primary lesions with a high propensity for ulceration. This is the first study to our knowledge that has profiled somatic mutations (c-KIT, BRAF, NRAS) in a multi-ethnic population of ALM patients and examined the histologic correlates of a “triple negative” genotype. This novel concept highlights the relevance of alternate pathways and molecular targets, such as PI3KCA in prognosis and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3591. doi:1538-7445.AM2012-3591