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Overexpression of Matrix Metalloproteinase 2 Predicts Unfavorable Outcome in Early-Stage Non-Small Cell Lung Cancer¹

Department of Surgery, Chirurgische Klinik und Poliklinik Klinikum Innenstadt, Ludwig-Maximilians University, 80336 Munich [B. P., W. S., R. S-H., O. T., W. M.]; Departments of Thoracic Surgery [B. P., W. S., O. T.] and Pathology [W. W.], Asklepios Fachkliniken München-Gauting, 82131 Gauting; and Division of Molecular Oncology, University Hospital Eppendorf, 20246 Hamburg [K. P.], Germany

This prospective study was performed to assess the impact of matrix metalloproteinase (MMP) 2 expression on the clinical course of patients with operable non-small cell lung cancer (NSCLC). Specimens of 193 consecutive patients with completely resected NSCLC were examined for MMP-2 expression by immunohistochemical staining with a polyclonal antibody. Homogeneous immunostaining of cancer cells was considered positive and heterogeneous, or no staining was considered negative concerning overexpression of MMP-2. Four specimens were excluded from further analyses because of unspecific staining. The median follow-up period was 71.5 months (range, 12–120 months). Overexpression of MMP-2 was observed in 64 (33.9%) of 189 patients and did not correlate with clinicopathological parameters. In patients without lymph node involvement (pN₀ stage) MMP-2 overexpression was an independent prognostic parameter for unfavorable outcome: Log-rank analysis showed a significant association of MMP-2 overexpression with shortened cancer-related survival (P = 0.04) and disease-free survival (P = 0.03). Multivariate regression analysis confirmed MMP-2 overexpression as predictor of shortened cancer-related survival in NSCLC without lymph node involvement (P = 0.005, relative risk, 2.6). The present study revealed that MMP-2 overexpression predicts a poor prognosis in early-stage NSCLC. Therefore, it might be worth investigating the role of MMP inhibitors as adjuvant therapeutic agents in NSCLC.

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