Reduced p21(WAF1/CIP1) expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder.
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.
Li
X
X
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Hui
A M
AM
Shi
Y Z
YZ
Takayama
T
T
Makuuchi
M
M
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
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53