title: Prognostic impact of matrix metalloproteinase-9 in operable non-small cell lung cancer.
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, <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.
authors.affiliation: Department of Surgery, Chirurgische Klinik-Innenstadt, University of Munich, Munich, Germany.
authors.forename: Wulf
authors.initials: W
authors.lastname: Sienel
authors.forename: Joe
authors.initials: J
authors.lastname: Hellers
authors.forename: Alicia
authors.initials: A
authors.lastname: Morresi-Hauf
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Wolf
authors.initials: W
authors.lastname: Mutschler
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
authors.forename: Bernward
authors.initials: B
authors.lastname: Passlick
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D020780:Matrix Metalloproteinase 9