title: MAP Kinase Pathways: Molecular Roads to Primary Acral Lentiginous Melanoma.
abstract: The etiology and pathogenesis of lentiginous acral melanomas are poorly understood. Recent studies have postulated that DNA repair mechanisms and cell growth pathways are involved in the development of melanoma, particularly changes in the MAPK pathways (RAS, BRAF, MEK 1/2, and ERK 1/2). The aim of this study is to assess the status of the MAP kinase pathways in the pathogenesis of acral melanomas. The authors examined the components of the RAS-RAF-MEK-ERK cascades by immunohistochemistry in a series of 16 primary acral melanomas by tissue microarray. The expression of MAP kinase cascade proteins changed in most cases. The authors observed that 57.14% of cases were BRAF positive and that 61.53%, 71.42%, and 71.42% of cases were positive for MEK2, ERK1, and ERK2, respectively; RAS was not expressed in 92.31%, and all cases were negative for MEK1. The absence of RAS and positivity for MEK2, ERK1, and ERK2 were most seen in invasive cases with high thickness. These aspects of the MAPK pathway require further examination in acral melanomas between different populations. Nevertheless, the results highlight significant alterations in the MAP kinase cascades that are related to histological indicators of prognosis in primary acral melanomas.
authors.affiliation: *Department of Dermatology, Medical School, Federal University of Bahia, Salvador, Brazil; †Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil; ‡Department of Pathology, Medical School, Federal University of Bahia, Salvador, Brazil; §AMO Oncological Clinic Care, Bahia, Brazil; ¶Department of Dermatology, Medical School, University of São Paulo, São Paulo, Brazil; and ‖Department of Surgical Pathology, Hospital Obrero, La Paz, Bolivia.
authors.forename: Juliana D
authors.initials: JD
authors.lastname: Fernandes
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hsieh
authors.forename: Luiz A R
authors.initials: LA
authors.lastname: de Freitas
authors.forename: Miguel A R
authors.initials: MA
authors.lastname: Brandao
authors.forename: Silvia V
authors.initials: SV
authors.lastname: Lourenço
authors.forename: Martin
authors.initials: M
authors.lastname: Sangueza
authors.forename: Marcello M S
authors.initials: MM
authors.lastname: Nico
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor