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The CDKN2A and MAP Kinase Pathways: Molecular Roads to Primary Oral Mucosal Melanoma.
MedLine Citation:
PMID:  23000904     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ABSTRACT:: The etiology and pathogenesis of oral mucosal melanomas are poorly understood, and no intraoral risk factors have been identified. Recent studies have postulated that DNA repair mechanisms and cell growth pathways are involved in the development of melanoma-particularly changes in the CDKN2A (p16-cyclinD-Cdk-pRb) and MAPK pathways (RAS, BRAF, MEK 1/2, and ERK 1/2 proteins). We examined the central components of the CDKN2A and RAS-RAF-MEK-ERK cascades by immunohistochemistry in a series of 35 primary oral melanomas by tissue microarray (TMA). We noted altered expression of the CDKN2A cascade proteins, although these modulations did not correlate significantly with clinical and pathological parameters. The expression of MAP kinase cascade proteins changed in most cases. We observed that 28.57% of cases were RAS-positive and that 82.85% and 74.28% of cases were positive for BRAF and ERK2, respectively; MEK2 and ERK1 were not expressed in 48.57% and 80% of cases, and all cases were negative for MEK1. The absence of RAS and ERK1 and positivity for BRAF and ERK2 were associated with higher histological grade, vascular invasion, and metastasis. Expression of MEK2 was significantly linked to vascular invasion (P = 0.043). The CDKN2A and MAPK pathways require further study in mucosal melanomas, but our results highlight the significance of important alterations, particularly with regard to histological indicators of poor prognosis in primary oral mucosal melanomas, independent of UV exposure.
Authors:
Ricardo Hsieh; Marcello M S Nico; Claudia M Coutinho-Camillo; Marcilei E Buim; Martin Sangueza; Silvia V Lourenço
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-20
Journal Detail:
Title:  The American Journal of dermatopathology     Volume:  -     ISSN:  1533-0311     ISO Abbreviation:  Am J Dermatopathol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7911005     Medline TA:  Am J Dermatopathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Dermatology Department, Medical School; and †Immunopathology Laboratory, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil ‡Surgical Pathology Department, Hospital AC Camargo, São Paulo, Brazil §Pathology Department, Hospital Obrero, La Paz, Bolívia ¶General Pathology Department, Dental School, University of São Paulo, São Paulo, Brazil.
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