title: BRAF mutations in metastatic malignant melanoma: comparison of molecular analysis and immunohistochemical expression.
abstract: Melanoma is a complex genetic disease, and multiple genetic alterations have been reported to play a role during disease progression. The dysregulation of BRAF signaling has been shown to affect many molecules that promote the continual progression of melanoma. Oncogenic BRAF expression plays a vital role in promoting cell invasion and metastasis in melanoma. It is also associated with poor prognosis in metastatic melanoma. About 40% to 60% of cutaneous melanomas have BRAF mutations, and 90% of the mutations involve a specific substitution at codon 600 (BRAF V600E). In this study, we compared BRAF (V600E) mutation detection by molecular analysis with BRAF expression by immunohistochemical (IHC) analysis using 2 different antibodies. A total of 25 metastatic malignant melanomas were included in this study. 10 of the 25 (40%) cases were positive by molecular analysis using the COBAS 4800 BRAF V600 Real-time PCR assay, and 18 of the 25 (72%) cases were positive by IHC analysis with 2 different antibodies. All positive cases by molecular analysis were positive by both IHC stains (100%). No false negatives were obtained with either IHC stain. Eight of the 25 (32%) were false-positive by both IHC stains. This study demonstrates that IHC analysis is a very sensitive test for evaluation of BRAF mutations in metastatic malignant melanoma and may be useful as an initial screening test.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA.
authors.forename: Laleh
authors.initials: L
authors.lastname: Ehsani
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Fisher
authors.forename: Momin T
authors.initials: MT
authors.lastname: Siddiqui
mesh_terms: D019943:Amino Acid Substitution; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf