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Annals of Oncology 13:1550-1557, 2002
© 2002 European Society for Medical Oncology


Original Paper

Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer

E. Laack1,+, A. Köhler1, C. Kugler2, T. Dierlamm1, C. Knuffmann1, G. Vohwinkel1, A. Niestroy1, N. Dahlmann3, A. Peters4, J. Berger5, W. Fiedler1 and D. K. Hossfeld1

1 Department of Oncology and Haematology, University Hospital Hamburg-Eppendorf; 2 Department of Surgery, 3 Department of Laboratory Medicine and 4 Department of Pathology, General Hospital Hamburg-Harburg; 5 Institute of Mathematics and Computer Science in Medicine, University Hospital Hamburg-Eppendorf, Germany

Received 17 December 2001; revised 5 April 2002; accepted 25 April 2002

Background:

Matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) are two proteins involved in angiogenesis. In the present study we investigated the association of pretreatment MMP-9 and VEGF serum levels with clinicopathological parameters and outcome in patients with non-small-cell lung cancer (NSCLC).

Patients and methods:

From February 1998 to October 1999, pretreatment serum levels of MMP-9 and VEGF were analysed in 118 patients with enzyme-linked immunoassays. At diagnosis 50 patients (42%) were staged as early disease (I/II), 27 patients (23%) as locally advanced (IIIA/IIIB), and 41 patients (35%) had metastatic disease (IV). In 72 of the 118 patients tumours were resected and 46 patients received combination chemotherapy with gemcitabine and vinorelbine.

Results:

The median survival of all 118 patients was 602 days. The 72 patients who had undergone surgery had a median survival of 972 days and the 46 patients who were treated with chemotherapy had a median survival of 298 days (P <0.001). Resected patients with stage I/II disease and an MMP-9 serum level <=1293 ng/ml or a VEGF serum level <=630 pg/ml had a significantly longer survival (median survival longer than 1218 days) than patients with higher serum levels (median survival 421 days) (P = 0.001 for MMP-9; P = 0.04 for VEGF). No significant difference in survival was observed in patients with resected stage III disease. Besides tumour stage, Karnofsky performance status and gender, the pretreatment serum level of MMP-9 was identified as an independent prognostic factor in a multivariate Cox regression analysis.

Conclusions:

Future studies may support our hypothesis that the pretreatment serum level of MMP-9 is a new powerful prognostic marker and can help to stratify NSCLC patients with stage I/II disease into low- and high-risk groups.

Key words: angiogenic factors, matrix metalloproteinase-9, non-small-cell lung cancer, prognostic factors, vascular endothelial growth factor


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