Prognostic effect of matrix metalloproteinase-9 in patients with resected Non small cell lung cancer

Abstract

Background: The role of tumor matrix metalloproteinase-9 (MMP-9) expression in non-small cell lung cancer (NSCLC) remains controversial. In this study, we investigated the prognostic value of tumor MMP-9 expression and other clinicopathologic factors in patients with completely resected NSCLC. Methods: This retrospective study included patients who underwent complete resection of pathological stage I-IIIA NSCLC at Severance Hospital, Seoul, Korea, between 1998 and 2009. Tumor samples of 417 patients were stained by immunohistochemistry, and the expression of MMP-9 in tumor cells was evaluated, using the median immunohistochemical score of 10 (range, 0-300) as the cut-off. Results: Tumor MMP-9 expression was observed in 161 (38.6%) of 417 patients. Log-rank analysis showed a significant association of tumor MMP-9 expression with shortened disease-free survival (p=0.01) but not with overall survival (p=0.109). Multivariate analysis demonstrated that tumor MMP-9 expression was not an independent prognostic factor of recurrence (p=0.142) or survival (p=0.807). However, among patients with adenocarcinoma, tumor MMP-9 expression was associated with relapse (p=0.003) and poor survival (p=0.033). Furthermore, tumor MMP-9 expression was an independent prognostic indicator of relapse in patients with adenocarcinoma (p=0.035). Conclusions: Among patients with NSCLC, tumor MMP-9 expression was associated with poor outcomes in those with adenocarcinoma, but not in those with squamous cell carcinoma. In addition, MMP-9 expression was identified as an independent predictor of relapse of completely resected lung adenocarcinoma.