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Tissue inhibitor of metalloproteinase 1 is an independent predictor of prognosis in patients with nonsmall cell lung carcinoma who undergo resection with curative intent
Author(s) -
Gouyer Valérie,
Conti Massimo,
Devos Patrick,
Zerimech Farid,
Copin MarieChristine,
Créme Evelyne,
Wurtz Alain,
Porte Henri,
Huet Guillemette
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20965
Subject(s) - medicine , matrix metalloproteinase , stage (stratigraphy) , lung cancer , carcinoma , oncology , lymph node , lung , pathology , clinical significance , tumor progression , cancer , tissue inhibitor of metalloproteinase , extracellular matrix , biology , paleontology , microbiology and biotechnology
BACKGROUND Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a role in the processes of extracellular matrix degradation. Changes in their expression levels have been observed in various tumor types, including lung carcinoma. However, their clinical significance and their prognostic importance in the progression of nonsmall cell lung carcinoma (NSCLC) remain to be specified. In this study, mRNA expression levels of MMP‐1, MMP‐9, TIMP‐1, and TIMP‐2 were evaluated in patients with resected NSCLC, and their associations with disease progression and prognosis were determined. METHODS Between June 1996 and December 1999, 116 patients underwent resection for NSCLC. Expression levels of MMPs and TIMPs were evaluated using Northern blot analysis in these NSCLC tissue samples and in 39 matched samples of normal lung tissue. RESULTS MMP‐1, MMP‐9, and TIMP‐1 expression levels were increased in tumor samples compared with matched, corresponding normal tissues. In contrast, TIMP‐2 expression was decreased in tumor samples. MMP‐1 tumor expression was correlated significantly with the evolution of lymph node status and tumor‐lymph node‐metastasis (TNM) stage. In contrast, MMP‐9 tumor expression was correlated significantly with increased T stage. TIMP‐1 overexpression was an independent predictor of worse survival in patients with NSCLC that was not associated with other prognosis factors, such as TNM stage. CONCLUSIONS The overexpression of TIMP‐1 was an independent prognostic marker in patients with NSCLC, and evaluating TIMP‐1 may be important for identifying patients who are at greater risk of disease recurrence. Cancer 2005. © 2005 American Cancer Society.