title: Expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) and its prognostic significance in resected non-small cell lung cancer.
abstract: OBJECTIVE
  Tissue inhibitor of metalloproteinase-3 (TIMP-3) inhibits the activity of metalloproteinases that play important roles in development and progression of malignant tumors. We conducted a retrospective study of TIMP-3 expression in resected non-small cell lung cancer (NSCLC).
  
  
  METHODS
  TIMP-3 expression was examined immunohistochemically in primary tumor specimens from 143 patients who underwent complete resection for NSCLC. Correlations between TIMP-3 expression grade and tumor histology, TNM classification, MMP-2 and MMP-9 expression grade, VEGF expression grade, intra-tumoral microvessel density, proliferative index, apoptosis index, and prognosis were analyzed.
  
  
  RESULTS
  TIMP-3 expression was low in 40, moderate in 71, and high in 32 patients. Higher TIMP-3 expression was seen in squamous cell carcinoma than in adenocarcinoma (P = 0.001), and reduced TIMP-3 expression was significantly associated with nodal involvement (P = 0.016) and advanced pathologic stage (P = 0.036). MMP-2 expression was reduced along with enhanced TIMP-3 expression (P = 0.010). The 5-year overall survival rates of low, moderate, and high TIMP-3 patients were 53, 64, and 84%, respectively (P = 0.037). Multivariate analysis confirmed that enhanced TIMP-3 expression was an independent factor for a favorable prognosis (P = 0.037).
  
  
  CONCLUSIONS
  TIMP-3 expression status was significantly correlated with pathologic stage and nodal involvement, and was an independent prognostic factor in resected NSCLC.
authors.affiliation: Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Mino
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Takenaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Sonobe
authors.forename: Ryo
authors.initials: R
authors.lastname: Miyahara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Otake
authors.forename: Hiromi
authors.initials: H
authors.lastname: Wada
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019717:Tissue Inhibitor of Metalloproteinase-3; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2