Tissue inhibitor of metalloproteinase 1 is an independent predictor of prognosis in patients with nonsmall cell lung carcinoma who undergo resection with curative intent.
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.
Gouyer
Valérie
V
Unité INSERM 560, Place de Verdun, Lille, France.
Conti
Massimo
M
Devos
Patrick
P
Zerimech
Farid
F
Copin
Marie-Christine
MC
Créme
Evelyne
E
Wurtz
Alain
A
Porte
Henri
H
Huet
Guillemette
G
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015152:Blotting, Northern; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1