Poster presentation, P141

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Study of mapk pathway components - Ras, Braf, Mek 1/2 and Erk 1/2 in series of 35 cases primary oral mucosal melanoma

BACKGROUND AND OBJECTIVES: Primary oral mucosal melanomas are rare, accounting for approximately 2% of all melanomas, with an incidence of 1.2 cases per 10 million per year. They are considered more aggressive and have a poorer prognosis than their cutaneous counterparts. According to the literature, there are well-established factors participating in the development and evolution of cutaneous melanomas, such as familial and environmental factors. However, the aetiology and pathogenesis of oral mucosal melanomas are poorly understood. Recent studies have reported somatic genetic alterations affecting the mitogen-activated protein kinase (MAPK) signalling pathway in the pathogenesis of cutaneous melanomas. This pathway comprises the Ras-Raf-MEK-ERK cascade and is considered an important regulator of melanoma cell proliferation, survival and differentiation. METHODS: To assess the status of the MAPK pathway in primary oral mucosal melanomas pathogenesis, our study examined the key components of Ras-Raf-MEK-ERK cascade by immunohistochemistry in a series of 35 primary oral melanomas organized in tissue microarray (TMA). RESULTS: Patients´ ages ranged from 9 to 91 years and the average age at time of diagnosis was 61 years old. There were 18 males (51.43%) and 17 (48.57%) females and the main prevalence of melanomas were amongst whites (21 patients or 75%) against non-whites (25%) (5 Black/ Afro-Brazilian, 2 Asian). The majority of the patients (71,42%) had palate lesions and invasive histopathological aspect (grade III) was observed in 80% of the specimens. Long distance metastasis was found in 60% of the cases. Expression of MAP kinase cascade proteins was altered in most cases. Ras was positive in 28,57% of the cases studied; Braf and ERK2 were overexpressed in most cases (82,85% and 74,28%, respectively); MEK2 and ERK1 were downregulated (48,57% and 80% of cases were negative, respectively) and MEK1 was not expressed in all cases. Downregulation of Ras and ERK1 and positivity for Braf and ERK2 were correlated with higher histological grade, vascular invasion and metastasis. Additionally, expression of MEK2 was statistically correlated with vascular invasion (p = 0.043). CONCLUSION: These results point to important alterations of Ras-Raf-MEK-ERK cascade and those are related to histological indicators of poor prognosis in primary oral mucosal melanomas, independent of the UV-exposition.

Advertisement from our sponsor: