Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53 in hepatocellular carcinomas.
To investigate the relationship between the expression of p21(WAF1/CIP1) protein and p53 status and the possible role of the two proteins in hepatocellular carcinomas (HCCs), we examined the expression of p21(WAF1/CIP1) and p53 immunohistochemically in 81 tumours from 65 patients with hepatocellular carcinoma. p21(WAF1/CIP1) protein was absent from 59 of 81 tumours (72.8%), and altered p53 expression was found in 43 (53.1%). p21(WAF1/CIP1) expression was significantly associated with p53 status (P = 0.0008); 38 of 59 tumours lacking p21(WAF1/CIP1) protein were accompanied by altered p53 expression. Further analyses showed that p21(WAF1/CIP1) expression was inversely correlated with p53 expression in hepatitis C virus (HCV)-related HCCs, but not in HBV-related hepatocellular carcinomas and hepatocellular carcinomas without viral infection. All 11 tumours with intrahepatic metastasis showed altered p21(WAF1/CIP1) or p53 expression. In contrast, no intrahepatic metastasis was found in any of the 17 tumours without abnormal expression of either of the two proteins. These results suggest that: (1) different modes of p21(WAF1/CIP1) regulation are involved in HCCs differing in their hepatitis viral infection status, and p21(WAF1/CIP1) expression appears to be predominantly related to altered p53 in HCV-related HCCs; (2) disruption of the p53-p21(WAF1/CIP1) cell-cycle-regulating pathway may contribute to malignant progression of HCC.
Shi
Y Z
YZ
Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan.
Hui
A M
AM
Takayama
T
T
Li
X
X
Cui
X
X
Makuuchi
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53