title: Expression of Fhit, Mlh1, and P53 protein in human gallbladder carcinoma.
abstract: There is limited information on the molecular changes involved in the pathogenesis of gallbladder carcinoma (GBC). The Fragile Histidine Triad (FHIT) gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in a variety of human malignancies. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins. We analyzed Fhit and Mlh1 protein expressions using immunohistochemical methods in 20 GBCs and three gallbladder adenomas (GBAs) to elucidate the role of Fhit protein in gallbladder carcinogenesis. In addition, we examined whether Fhit and Mlh1 protein expressions correlated with P53 expression and clinicopathological findings. Significant loss or reduction in Fhit expression was noted in nine (45%) of the GBCs and one of the GBAs. Loss of Mlh1 protein expression was detected in six (30%) of the GBCs and one of the GBAs. Reduced Fhit expression was significantly associated with the absence of Mlh1 protein expression in the GBCs and the GBAs (p=0.0186). P53 overexpression was present in 11 (55%) of the GBCs, but none of the GBAs. Fhit and Mlh1 protein expressions were not significantly associated with P53 expression and clinicopathological findings. These results suggested that reduced Fhit expression might be involved in the development of GBC and be correlated with Mlh1 expression.
authors.affiliation: Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, 36-1 Nishi-machi, Yonago 683-8504, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Koda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yashima
authors.forename: Koichirou
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Andachi
authors.forename: Akihide
authors.initials: A
authors.lastname: Hosoda
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Murawaki
mesh_terms: D017766:Acid Anhydride Hydrolases; D048868:Adaptor Proteins, Signal Transducing; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins; D002454:Cell Differentiation; D004260:DNA Repair; D005260:Female; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D000099170:Bis(5'-adenosyl)triphosphatase; C501486:MLH1 protein, human