BRAF Mutation Analysis in Primary Mucosal Melanoma of the Head and Neck – A Multi-Institutional Analysis of 66 Cases
Ellen Aquino, Beverly Y Wang, Guorong Chen, Liang Wu, Honggang Liu, Qian Yao, Mai Gu. University of California Irvine Medical Center, Orange, CA; Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY; Wenzhou Medical College, Wenzhou, Zhejiang, China; Tongren Hospital, Capital Medical University, Beijing, China
Background: Primary mucosal melanoma is a highly aggressive rare disease of unknown etiology, unlike its cutaneous counterpart in which sun exposure is generally accepted as a major causative factor. Approximately 50% of cutaneous melanomas harbor BRAF mutations involved in the MAP kinase/ERK-signaling pathway. This becomes the oncologic target for a selective and potent inhibitor of mutant BRAF, vemurafenib (Zelboraf). However, BRAF mutation has not been extensively studied in the primary mucosal melanoma of the head and neck primarily due to its low incidence comparing with the cutaneous melanoma.
Design: A multi-institutional collaboration is conducted to collect all primary mucosal melanomas of the head and neck. Unstained slides (5 µm) were cut from the formalin-fixed and paraffin-embedded tissue blocks. All sections contained more than 50% of tumor. BRAF mutation status was analyzed by FDA approved Cobas 4800 BRAF V600 Mutation Test kit. Clinical and pathological parameters were also analyzed.
Results: Seventy-two patients were identified during April 2000 – December 2011. The diagnoses were confirmed on H&E with or without immunohistochemical studies by four pathologists independently (GC, LW, HL, and QY). Invalid results were obtained in six patients after repeat and extraction, and therefore were excluded from the study. In four of the six cases with invalid results, melanin pigments were abundant covering over 50% of the tumor. Among 66 patients with valid results, there were 29 men and 37 women with an average age of 65.2 years (range 39–97 years). The anatomic sites included sinonasal/oral cavity in 53 patients and various sites within the eyes (excluding cutaneous eyelid) in 13 patients. BRAF V600E mutation in exon 15 was identified in 3 patients (4.5%), one of conjunctiva, one of cornea, and one of nasal cavity.
Conclusions: Unlike in cutaneous melanoma, BRAF mutation is much less frequently detected in primary mucosal melanoma of the head and neck (4.5%). This indicates that different etiologic pathways play a role in the pathogenesis of these tumors. The current personalized targeted therapy with vemurafenib (Zelboraf) may not be as effective for this rare deadly disease. Other possible molecular targets in mucosal melanoma need to be investigated.
Category: Head & Neck
Monday, March 4, 2013 2:45 PM
Proffered Papers: Section F, Monday Afternoon