EXPRESSION OF P-GLYCOPROTEIN AND P53 IN ADVANCED HEPATOCELLULAR-CARCINOMA TREATED BY SINGLE-AGENT CHEMOTHERAPY - CLINICAL CORRELATION

Hepatocellular carcinoma (HCC), a chemoresistant tumour, is the most c ommon fatal cancer in Taiwan. Hepatocellular carcinoma frequently expr esses a high level of P-glycoprotein (P-gp), which is a specific pheno type of a multidrug-resistance gene, and harbours mutations of the tum our suppressor gene p53. A modulatory relationship between p53 and P-g p has been reported. In this study, we analysed the expression of P-gp in relation to chemotherapeutic response and p53 protein expression i n advanced HCC. Prechemotherapeutic tumour samples were obtained from 25 patients with HCC which had been treated with either etoposide (VP- 16) or doxorubicin. P-glycoprotein and p53 in HCC were visualized by i mmunohistochemical staining using the monoclonal antibodies JSB-1 and DO1, respectively. We investigated the correlation of P-gp expression with chemotherapeutic responses, clinicopathological features and p53 protein expression. In our study, seven cases achieved partial remissi on, and the remaining 18 cases had a poor response to chemotherapy. Ex pression of P-gp was observed in 13 rumours (52%). Positive P-gp prote in expression was significantly associated with non-responders (8% or 1/13 vs 50% or 6/12, P = 0.03). Thus, P-gp expression inversely correl ated with chemotherapeutic response. Expression of p53 protein was see n in 12 cases and did not correlate with chemosensitivity or P-gp expr ession. In summary, P-gp expression correlates with the chemosensitivi ty of HCC that has been treated with VP-16 or doxorubicin and p53 muta tions do not appear to be a major determinant of P-gp expression in ad vanced HCC.