The expression of P-glycoprotein and multidrug resistance proteins 1 and 2 (MRP1 and MRP2) in human malignant mesothelioma.

BACKGROUND Malignant mesothelioma is a malignancy with a primary resistance to chemo- and radiotherapies for reasons which are still unclear. Multidrug resistance proteins might explain the observed resistance, but no studies have assessed their expression in mesothelioma. PATIENTS AND METHODS Immunohistochemical expression of P-glycoprotein (P-gp), and the multidrug resistance proteins 1 and 2 (MRP1 and MRP2) were investigated in 36 cases of malignant mesothelioma and in samples from normal mesothelium. RESULTS P-gp immunopositivity was found in 61%, MRP1 immunopositivity in 58% and MRP2 positivity in 33% of the cases. Normal mesothelium did not express these multidrug-resistant proteins. There was a significant association between P-gp and MRP2 (P = 0.022) expression. No or weak P-gp, MRP1 or MRP2 immunostaining was significantly more frequent in sarcomatoid mesothelimas than in epithelial or biphasic mesotheliomas (P = 0.031, P = 0.034 and P = 0.024, respectively). There was no significant association between patient survival and expression of the multidrug-resistant proteins. CONCLUSIONS The results show that P-gp, MRP1 and MRP2 are induced and expressed in malignant mesothelial cells. Regardless of their expression no association with survival of the patients was seen, suggesting that the primary resistance of malignant mesotheliomas is not solely dependent on their expression or function.