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Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer

2002; Wiley; Volume: 103; Issue: 5 Linguagem: Inglês

10.1002/ijc.10841

1097-0215

Wulf Sienel, Joe Hellers, Alicia Morresi‐Hauf, Ralf Lichtinghagen, W. Mutschler, Marianne Jochum, Christoph A. Klein, Bernward Passlick, Klaus Pantel,

Cell Adhesion Molecules Research

Abstract We assessed the clinical impact of MMP‐9 expression on long‐term survival in patients with operable non‐small cell lung cancer (NSCLC). Primary tumors of 143 consecutive patients with NSCLC resected completely and without overt distant metastases (pT1‐4, pN0‐2, M0, R0) were examined for MMP‐9 expression using immunohistochemistry with a polyclonal, affinity‐purified rabbit antibody that recognizes both latent and active MMP‐9. Immunohistochemical staining of tumor cells was evaluated in comparison to normal bronchiolar epithelium that served as an internal positive control. MMP‐9 expression was categorized into negative, ≤5% tumor cells stained; heterogeneous, >5% and <95% tumor cells stained; and homogeneous, ≥95% tumor cells stained at least as intensively as bronchiolar epithelium. The median follow‐up period was 72 months (range = 12–144 months). Homogeneous expression of MMP‐9 was observed in 26 of 143 patients (18.2%) and did not correlate with clinicopathological parameters. Relapse defined as diagnosis of distant metastasis or local recurrence was observed in 78 of the 130 (60%) patients eligible for clinical follow up analysis. Relapse led to cancer‐related death in all of the 78 patients within the observation period. Kaplan‐Meier analysis showed a significant association between homogeneous MMP‐9 expression and shortened cancer‐related survival (log‐rank p = 0.016). Multivariate regression analysis including pT‐status, pN‐status, tumor histology and tumor grading showed an independence of this prognostic impact of homogeneous MMP‐9 expression ( p = 0.045). Thus, immunohistochemical evaluation of MMP‐9 expression may provide a basis for the preselection of patients to be included in trials investigating specific protease inhibitor therapy after surgical resection of NSCLC. © 2002 Wiley‐Liss, Inc.