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

Int J Cancer. 2003 Feb 20;103(5):647-51. doi: 10.1002/ijc.10841.


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, <or=5% tumor cells stained; heterogeneous, >5% and <95% tumor cells stained; and homogeneous, >or=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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Lymph Nodes / pathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Rate


  • Matrix Metalloproteinase 9