Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Matrix metalloproteinases ( MMPs), in particular the gelatinases (MMP-2 and - 9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma ( MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM ( n = 35), inflamed pleura (IP, n = 12) and uninflammed pleura ( UP, n = 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan - Meier and Cox proportional hazard models. In MM, pro- and active MMP-2 levels were significantly greater than for MMP-9 ( P = 0.006, P<0.001). Active MMP-2 was significantly greater in MM than in UP ( P = 0.04). MMP-2 activity was equivalent between IP and MM, but both pro- and active MMP-9 activities were greater in IP ( P = 0.02, P = 0.009). While there were trends towards poor survival with increasing total and pro- MMP-2 activity ( P = 0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss ( pro- MMP-2 P = 0.03, total MMP-2 P = 0.04). Total and pro- MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM.