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 resistanc e to chemo- and radiotherapies for reasons which are still unclear. Multidr ug resistance proteins might explain the observed resistance, but no studie s have assessed their expression in mesothelioma. Patients and methods: Immunohistochemical expression of P-glycoprotein (P-g p), and the multidrug resistance proteins 1 and 2 (MRP1 and MRP2) were inve stigated in 36 cases of malignant mesothelioma and in samples from normal m esothelium. Results: P-gp immunopositivity was found in 61%, MRP1 immunopositivity in 5 8% and MRP2 positivity in 33% of the cases. Normal mesothelium did not expr ess 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 MRP 2 immunostaining was significantly more frequent in sarcomatoid mesothelima s than in epithelial or biphasic mesotheliomas (P = 0.031, P = 0.034 and P = 0.024, respectively). There was no significant association between patien t survival and expression of the multidrug-resistant proteins. Conclusions: The results show that P-gp, MRP1 and MRP2 are induced and expr essed in malignant mesothelial cells. Regardless of their expression no ass ociation with survival of the patients was seen, suggesting that the primar y resistance of malignant mesotheliomas is not solely dependent on their ex pression or function.