SAN FRANCISCOThe biologic marker matrix metalloproteinase-9
(MMP-9) has been identified as an important new predictor of disease recurrence
and poor outcome in non-small-cell lung cancer (NSCLC). It also offers some
insight into the mechanisms by which NSCLC tumors grow and spread.
Eckart Laack, MD, of the University Hospital Hamburg-Eppendorf, Hamburg,
Germany, reported the results at the 37th Annual Meeting of the American
Society of Clinical Oncology (ASCO abstract 1645). The study involved 118 NSCLC
patients (50 with stage I/II disease, 27 with stage IIIA/B disease, and 41 with
stage IV disease).
The investigators measured pretreatment serum levels of two factors, both of
which play an important role in the angiogenic process: (1) MMP-9, which
degrades basement membrane type IV collagen, allowing angiogenesis and, by
implication, tumor invasion and metastasis, and (2) vascular endothelial growth
factor (VEGF), the most potent growth factor and a positive regulator of
angiogenesis in a majority of malignancies.
The study showed that serum levels of MMP-9 were significantly correlated
with tumor stage. Patients with early disease had a median MMP-9 level of 910 ng/mL, compared with 1,340 ng/mL for those with locally advanced disease and
1,796 ng/mL for those with metastatic disease (P = .005).
Patients who died during the first year had significantly higher
pretreatment levels of MMP-9 (1,796 ng/mL) than those who survived 1 year (989
ng/mL, P = .0005).
The median serum level for MMP-9 for all patients was 1,293 ng/mL. Levels of
MMP-9 in excess of 2,300 ng/mL carried a very poor prognostic indication, Dr.
Laack said. These patients had a median survival of 278 days vs 587 days for
those with levels less than 1,200 ng/mL.
Besides performance status, the only independent prognostic factor in
multivariate analysis was the pretreatment serum level of MMP-9. Stage,
histologic type, sex, age, and lactate dehydrogenase, hemoglobin, and VEGF levels had no effect on survival.