title: Immunohistochemical study of DPC4 and p53 proteins in gallbladder and bile duct cancers.
abstract: Gallbladder and bile duct carcinomas belong to the family of biliary tract tumors, but they demonstrate different clinical behavior. We evaluated a series of biliary tract carcinomas to determine whether they also had genotypic differences by analysis of the tumor suppressor genes DPC4 and p53. Twenty-one gallbladder cancers, 20 intrahepatic bile duct carcinomas, and 10 extrahepatic bile duct carcinomas were retrieved from the surgical pathology files of Kaohsiung Medical University Hospital. Sections were immunostained with monoclonal antibodies to the DPC4 and P53 proteins. Statistical differences between gallbladder cancer and bile duct carcinomas were determined using chi2 analysis or the Fisher's exact test, when appropriate. Two of the 21 gallbladder cancers (9.5%), 7 of the 20 intrahepatic bile duct carcinomas (35%), and five of the 10 extrahepatic bile duct carcinomas (50%) were negatively labeled for DPC4. The differences were significant between gallbladder carcinoma and both intrahepatic bile duct carcinomas (p = 0.023) and extrahepatic bile duct carcinomas (p = 0.012). A higher frequency of P53 overexpression was found in gallbladder cancers (61.9%) than in intrahepatic bile duct carcinomas (26.3%) (p = 0.024). This study suggests that the DPC4 gene may play a limited role in gallbladder carcinoma; however, p53 gene mutation is more frequently found in gallbladder cancers. In contrast, DPC4 deletion may be more common in bile duct carcinomas, especially in those arising from the extrahepatic bile duct. These findings support the concept that gallbladder and bile duct carcinomas are different tumors with differing etiologies and tumorigenesis.
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, 807, Kaohsiung, Taiwan.
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Chuang
authors.forename: King-Teh
authors.initials: KT
authors.lastname: Lee
authors.forename: Kun-Bow
authors.initials: KB
authors.lastname: Tsai
authors.forename: Pai-Ching
authors.initials: PC
authors.lastname: Sheen
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism*; D017734:Bile Ducts, Extrahepatic; D001653:Bile Ducts, Intrahepatic; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53