title: B-Raf mutations, microsatellite instability and p53 protein expression in sporadic basal cell carcinomas.
abstract: Basal Cell Carcinoma (BCC) is the most common skin malignancy. Genes related to the Ras/Raf signalling pathway have been implicated in the pathogenesis of skin cancer. The objective of this study was to investigate the presence of B-Raf mutations in sporadic BCCs as well as its correlation with the phenotype of microsatellite instability (MSI), the clinicopathological parameters of the tumours and p53 protein expression. 83 BCC specimens were screened for B-Raf mutations, applying polymerase chain reaction, single-stranded conformation polymorphism (PCR-SSCP) and DNA sequencing. MSI status was examined using mononucleotide microsatellite markers and p53 protein expression was demonstrated by immunohistochemical staining. A C to T transition at 1790 nucleotide leading to a silent mutation L597L; and a T to A transversion causing an amino acid change (F610I) have been found. MSI was detected in 5% of the cases and p53 accumulation was present in 37/83 samples studied. Although rare B-Raf alterations have been observed in BCC, none of them harboured the hot-spot mutation T1799A commonly present in melanomas and colon carcinomas. Consequently, no correlation could be determined between B-Raf alterations, MSI status, the clinicopathological features and p53 protein expression. Our results are in favour of a secondary importance for Ras signalling cascade genes in BCC pathogenesis.
authors.affiliation: 1st Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. agstam@med.uoa.gr
authors.forename: Angeliki
authors.initials: A
authors.lastname: Stamatelli
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Thaleia
authors.initials: T
authors.lastname: Bei
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Nicolaos V
authors.initials: NV
authors.lastname: Michalopoulos
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Kiriaki
authors.initials: K
authors.lastname: Aroni
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf