title: High-level microsatellite instability is not involved in gallbladder carcinogenesis.
abstract: The molecular alterations involved in the pathogenesis of gallbladder cancer are not yet well defined. Our aim was to determine the microsatellite status of gallbladder carcinomas and its possible correlation with alterations in K-ras and p53 genes as well as the clinicopathological characteristics of these tumors. A group of 37 gallbladder carcinomas was analyzed for alterations in a proposed panel of mononucleotide and dinucleotide markers of microsatellite instability. Somatic frameshift mutations at repeated sequences in the coding regions of TGF-betaRII, Bax, hMSH3, hMSH6 were also examined. The findings were correlated with the presence of K-ras and p53 alterations, and tumors' clinicopathological features. Microsatellite instability and/or LOH was observed in 9 gallbladder carcinomas. Cases showing microsatellite instability displayed alterations only in dinucleotide markers and were classified as MSI-L carcinomas. A subset of gallbladder carcinomas is characterized by low-level instability, based on the analysis of the above mentioned panel of markers. The pathway of microsatellite instability seems to play a minor role in the pathogenesis of gallbladder cancer.
authors.affiliation: Department of Pathology, Medical School, The National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece. asaetta@med.uoa.gr
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Fanie
authors.initials: F
authors.lastname: Gigelou
authors.forename: Pollyanthi I
authors.initials: PI
authors.lastname: Papanastasiou
authors.forename: Stavroula V
authors.initials: SV
authors.lastname: Koilakou
authors.forename: Harikleia
authors.initials: H
authors.lastname: Kalekou-Greca
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Miliaras
authors.forename: Nikolaos V
authors.initials: NV
authors.lastname: Michalopoulos
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005706:Gallbladder Neoplasms / Q000235:genetics*; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor