title: Reduced p21(WAF1/CIP1) expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder.
abstract: The molecular basis underlying the development and progression of gallbladder carcinoma (GBC) remains poorly understood. To evaluate the roles of p21(WAF1/CIP1) and p53 in gallbladder carcinogenesis and to assess their prognostic significance for patients with GBC, we used immunohistochemistry to examine the expression of p21(WAF1/CIP1) and p53 protein in a series of surgically resected specimens, including normal epithelia, precancerous lesions adenoma, and dysplasia, and carcinomas of the gallbladder. Reduced p21(WAF1/CIP1) expression was frequently observed in carcinomas (18 of 37 lesions; 49%), and even in precancerous lesions adenomas (3 of 7; 43%) and dysplasias (5 of 5; 100%). p53 overexpression was detected in 43% of the adenomas, 60% of the dysplasias and 57% of the carcinomas. There was an inverse relationship between p21(WAF1/CIP1) and p53 expression in GBCs (P =.01). Survival analysis indicated that reduced p21(WAF1/CIP1) expression was significantly associated with shortened disease-free and overall survival (P =.04 and.03, respectively) for patients with stages II to IV GBCs. These observations suggest that reduced p21(WAF1/CIP1) expression and p53 overexpression contribute to GBC from an early stage and that determination of p21(WAF1/CIP1) expression in surgically resected specimens would add prognostic information to conventional pathologic examinations for patients with advanced-stage GBC.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: A M
authors.initials: AM
authors.lastname: Hui
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Shi
authors.forename: T
authors.initials: T
authors.lastname: Takayama
authors.forename: M
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53