Ya-Zhou Shi

Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53 in hepatocellular carcinomas.

To investigate the relationship between the expression of p21WAF1/CIP1 protein and p53 status and the possible role of the two proteins in hepatocellular carcinomas (HCCs), we examined the expression of p21WAF1/CIP1 and p53 immunohistochemically in 81 tumours from 65 patients with hepatocellular carcinoma. p21WAF1/CIP1 protein was absent from 59 of 81 tumours (72.8%), and altered p53 expression was found in 43 (53.1%). p21WAF1/CIP1 expression was significantly associated with p53 status (P= 0.0008); 38 of 59 tumours lacking p21WAF1/CIP1 protein were accompanied by altered p53 expression. Further analyses showed that p21WAF1/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 p21WAF1/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 p21WAF1/CIP1 regulation are involved in HCCs differing in their hepatitis viral infection status, and p21WAF1/CIP1 expression appears to be predominantly related to altered p53 in HCV-related HCCs; (2) disruption of the p53–p21WAF1/CIP1 cell- cycle-regulating pathway may contribute to malignant progression of HCC.

Loss of p16INK4 protein, alone and together with loss of retinoblastoma protein, correlate with hepatocellular carcinoma progression

To investigate the role of p16(INK4) protein absence in hepatocellular carcinoma progression, we examined p16(INK4) expression immunohistochemically in 81 primary and 23 metastatic lesions of hepatocellular carcinoma, in which retinoblastoma protein status had been determined. p16(INK4) protein was absent from 44% of the total of 104 tumors. The rate of p16(INK4) absence was twice as high in metastatic lesions (74%) compared with primary lesions (36%) (P=0.001). Loss of p16(INK4) and/or retinoblastoma protein was significantly associated with decreased tumor differentiation, vascular invasion and metastasis. In conclusion, p16(INK4) protein absence, alone and together with loss of retinoblastoma protein, contributes to hepatocellular carcinoma progression.

Telomerase expression and p53 status in hepatocellular carcinoma.

OBJECTIVES:Genomic instability is a driving force for tumorigenesis. Telomerase and p53 play central roles in maintaining genomic integrity. The purpose of this study was to assess the role of telomerase expression and p53 protein overexpression in hepatocellular carcinoma (HCC).METHODS:Telomerase activity and p53 overexpression were investigated in 63 patients undergoing hepatectomy for HCC by a telomeric repeat amplification protocol and immunohistochemistry, respectively. The associations among telomerase expression, p53 overexpression, and clinicopathological features were analyzed, and independent prognostic factors in the recurrence of HCC after hepatectomy were determined.RESULTS:Telomerase expression did not correlate with clinicopathological features except hepatitis virus status (p = 0.04) and was identified as a significant prognostic variable for HCC recurrence (p = 0.027) along with portal venous invasion (p = 0.001). In contrast, p53 overexpression strongly correlated with tumor differentiation (p < 0.0001) but did not reflect time to recurrence (p = 0.26). Telomerase expression did not correlate with p53 overexpression (p = 0.35).CONCLUSIONS:The reactivation of telomerase was of significant value in predicting the recurrence of HCC after hepatectomy. However, p53 overexpression did not correlate with telomerase expression in HCC, nor did it reflect the time to recurrence.

Proliferative marker Ki-67 in gallbladder carcinomas: high expression level predicts early recurrence after surgical resection

To evaluate the prognostic value of proliferative maker Ki-67, its expression was determined immunohistochemically in 37 gallbladder carcinomas (GBCs). A high Ki-67 index was significantly correlated with tumor lymphatic invasion (P=0.007) and vascular invasion (P=0.04). High Ki-67 index group and low Ki-67 index group showed different clinical courses. Five patients who experienced recurrences in high Ki-67 index group developed their recurrent diseases within one year after surgery and died soon after recurrence, while the recurrences (five cases) in low Ki-67 index group were distributed all stages after surgery. In conclusion, high Ki-67 index predicts early recurrence after surgery for GBCs.

Altered p21WAF1/CIP1 expression is associated with poor prognosis in extrahepatic bile duct carcinoma

Abstract This study was designed to determine the clinical implications of p21WAF1/CIP1 expression and the relationship between p21WAF1/CIP1 expression and p53 status in extrahepatic bile duct carcinoma (EBDC). Low p21WAF1/CIP1 expression was immunohistochemically detected in 23 (67.6%) of 34 EBDCs, moderate in six (17.7%), and high in five (14.7%). Kaplan–Meier curves showed that low and high p21WAF1/CIP1 expressions were significantly associated with shortened disease-free survival (low vs. moderate, P=0.02; high vs. moderate, P=0.01). There was no correlation between p21WAF1/CIP1 and p53 expression. These findings suggest that altered p21WAF1/CIP1 expression exerts an adverse influence on the prognosis of EBDC.