Increased expression of matrix metalloproteinase-2 -MMP-2- predicts tumour recurrence and unfavourable outcome in non-small cell lung cancer

Abstract

The purpose of this study was to analyse the expression of matrix metalloproteinase-2 (MMP-2) and its extracellular matrix metalloproteinase inducer (EMMPRIN) in non-small cell lung cancer (NSCLC), and to evaluate their significance to predict tumour behaviour. The study consists of 212 patients treated by the resection of the tumour. Tumour samples were stained immunohistochemically, and the expression of MMP-2 and EMMPRIN was evaluated both in tumour cells and in peritumoural stromal tissue. The results were compared with clinicopathological factors and survival of the patients. High expression of MMP-2 in tumour cells was found in 83 out of 191 cases (44%). Adenocarcinomas showed more often high expression of MMP-2 as compared with squamous cell or large cell carcinomas (p=0.001). High cancer cell associated MMP-2 expression was associated with increased tumour recurrence (p=0.001). Tumour stroma showed positive staining in 162 (98%) cases and was considered highly stained in 120 (72%) cases. The high stromal MMP-2 expression was noticed more often among large cell carcinomas as compared with other histological types (p=0.007). High cancer cell associated EMMPRIN expression was found in 115 (61%) cases and was associated only with high MMP-2 expression in tumour cells (p=0.006). In overall survival (OS) and disease free survival (DFS) analyses, type of tumour (p=0.001 and p=0.0004), advanced stage (p=0.001 and p=0.013) and high MMP-2 expression in tumour cells (p=0.018 and p=0.001) were associated with poor survival. Also, high stromal MMP-2 expression was related to poor outcome in both OS and DFS analyses (p=0.010 and 0.045, respectively). In multivariate analysis, stromal MMP-2 expression retained its prognostic value to predict OS and DFS (p=0.028 and p=0.039, respectively), together with tumour type and stage (p=0.017, p=0.001 and p=0.021, p=0.008, respectively). The present study shows the significant prognostic value of MMP-2 in NSCLC suggesting that the use of MMP-2 is valuable in determining the patients with more aggressive disease.