Author(s): Uribe P, Andrade L, Gonzalez S
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Abstract The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase signaling pathway can be activated through mutations of V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) oncogene, frequently found in melanoma (60\%), common nevi (CN) (73-82\%), and atypical nevi (AN) (52-80\%). MAPK activation has been reported between 0 and 22\% in nevi, and 86\% of primary melanoma, without any knowledge of BRAF mutational status. We studied the correlation of MAPK activation status, BRAF mutation, and B-Raf expression in CN, AN, and melanoma. Using immunohistochemistry, phosphorylated (active) MAPK and B-Raf expression was studied in 24 CN, 21 AN, and 26 primary cutaneous melanomas (PM). BRAF mutations at codon 600 were assessed by PCR-RFLP. Active MAPK was detected in 29\% of CN, 48\% of AN, and 85\% of PM. BRAF mutation was found in 67\% of CN, 62\% of AN, and 58\% of PM. In all, 23\% of CN, 54\% of AN, and 93\% of PM with BRAF mutation have activated MAPK. All lesions expressed B-Raf. BRAF mutation does not seem to be sufficient to produce MAPK activation in melanocytic nevi, and it is suggested that other events are needed to induce MAPK activation, that is, B-Raf overexpression, inhibition of MAPK phosphatases, or suppression of RAF kinase inhibitors.
This article was published in J Invest Dermatol
and referenced in Journal of Addiction Research & Therapy