Expression of P‐glycoprotein and p53 in advanced hepatocellular carcinoma treated by single agent chemotherapy: Clinical correlation

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Abstract
Hepatocellular carcinoma (HCC), a chemoresistant tumour, is the most common fatal cancer in Taiwan. Hepatocellular carcinoma frequently expresses a high level of P‐glycoprotein (P‐gp), which is a specific phenotype of a multidrug‐resistance gene, and harbours mutations of the tumour suppressor gene p53. A modulatory relationship between p53 and P‐gp has been reported. In this study, we analysed the expression of P‐gp in relation to chemotherapeutic response and p53 protein expression in 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 immunohistochemical 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 remission, and the remaining 18 cases had a poor response to chemotherapy. Expression of P‐gp was observed in 13 tumours (52%). Positive P‐gp protein expression was significantly associated with non‐responders (8% or 1/13 vs 50% or 6/12, P= 0.03). Thus, P‐gp expression inversely correlated with chemotherapeutic response. Expression of p53 protein was seen in 12 cases and did not correlate with chemosensitivity or P‐gp expression. In summary, P‐gp expression correlates with the chemosensitivity of HCC that has been treated with VP‐16 or doxorubicin and p53 mutations do not appear to be a major determinant of P‐gp expression in advanced HCC.