Expression and prognostic significance of catalase in malignant mesothelioma

BAGKGROUND. Free radicals and antioxidant enzymes (AOEs) may play a critica l role in cell proliferation and in the resistance of malignant cells again st cytotoxic drugs and radiation. Malignant mesothelioma is a resistant tum or with high levels of manganese superoxide dismutase, a central superoxide scavenging AGE. In the current study, the authors assessed the expression and prognostic role of catalase, an important hydrogen peroxide scavenging AGE, in malignant pleural mesothelioma. METHODS, Catalase expression tvas investigated by immunohistochemistry in 5 cases of nonmalignant healthy pleura and in tumor tissue of 32 mesotheliom a patients, and by Western blot in 7 continuous human mesothelioma cell lin es. The distribution of catalase in mesothelioma cells was assessed by immu noelectron microscopy. Furthermore, to investigate the effect of catalase i nhibition in the drug resistance of these cells in vitro, the authors expos ed mesothelioma cells with the highest catalase level to epirubicin with an d without aminotriazole pretreatment. RESULTS. Nonmalignant mesothelial cells showed no catalase immunoreactivity whereas most mesothelioma cases (24 of 32, 75%) were catalase positive, 17 cases (53%) showing moderate or high expression. Higher catalase expressio n in mesothelioma was associated with a better prognosis, mean survival rat e from diagnosis being 6 and 24 months for negative/low expression and mode rate/high expression, respectively. Furthermore, a coordinately high expres sion of both manganese-superoxide dismutase (Mn-SOD) and catalase predicted even more favorable outcome of the mesothelioma patients. Catalase also co uld be detected in all mesothelioma cell lines, the most resistant cell lin e showing the highest protein expression and compartmentalization of catala se mainly to peroxisomes. Aminotriazole inhibition of catalase had a margin al effect on the toxicity caused by epirubicin. CONCLUSIONS. Catalase may have multifactorial effects in malignant cells; h igh catalase and/or coordinated high expression of Mn-SOD and catalase may decrease tumor progression by modulating the cellular redox state, but enha nced antioxidant capacity of mesothelioma cells also may protect tumor cell s against exogenous oxidants, at least in vitro. (C) 2001 American Cancer S ociety.