Lack of association between BRAF mutation and MAPK ERK activation in melanocytic nevi.
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.
Uribe
Pablo
P
Department of Pathology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Andrade
Leonardo
L
Gonzalez
Sergio
S
D003062:Codon / Q000235:genetics; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000378:metabolism*; D009154:Mutation; D009508:Nevus, Pigmented / Q000201:enzymology* / Q000235:genetics; D010766:Phosphorylation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics
D003062:Codon; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases