1. ¹University Department of Medical Oncology, Osborne Building, Leicester Royal Infirmary, Leicester LE1 5WW, UK
2. ²Department of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital NHS Trust, Groby Road, Leicester LE3 9QP, UK
3. ³Department of Obstetrics and Gynaecology, University of Leicester, Robert Kilpatrick Building, Leicester Royal Infirmary, Leicester LE1 5WW, UK
4. ⁴Department of Pathology, University of Leicester, Robert Kilpatrick Building, Leicester Royal Infirmary, Leicester LE1 5WW, UK

Correspondence: Dr KJ O'Byrne, E-mail: ken.obyrne@uhl-tr.nhs.uk

Received 6 September 2002; Revised 17 February 2003; Accepted 26 February 2003.

Abstract

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.