title: The prognostic role of tissue and serum MMP-1 and TIMP-1 expression in patients with non-small cell lung cancer.
abstract: OBJECTIVE
  Matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) play an important role in tumor invasion and progression. The aim of this study was to evaluate the prognostic role of MMP-1 and TIMP-1 in non-small cell lung cancer (NSCLC). To find out a potential serum biomarker, tissue and serum levels were investigated together.
  
  
  METHODS
  For 85 surgically resected NSCLC patients who had pre-operative serum samplings, MMP-1 and TIMP-1 expression were investigated using immunohistochemistry in tumor tissue and ELISA in serum. Tumor cells and surrounding stromal cells were assessed separately.
  
  
  RESULTS
  Higher expression of MMP-1 in tumor cells comparing to stromal cells was related to male gender (P=0.006), ever smoker (P=0.004), and pooly differentiated tumor (P=0.043). For TIMP-1, adenocarcinoma showed higher tumor cell expression, while squamous cell carcinoma showed higher stromal expression (P=0.007). Patients with high carcinoembryonic antigen (CEA) level, the presence of vascular invasion, recurrence or death showed higher serum MMP-1 level. There was no correlation between the tissue and serum levels of MMP-1 and TIMP-1. A tumor/stroma TIMP-1 intensity ratio ≥1 was strongly associated with early recurrence in multivariate analysis (hazard ratio=280.55, 95% confidence intervals; 11.12-7080.45; P=0.001). High serum MMP-1 (≥3,500pg/ml) showed a trend for short overall survival (P=0.080). When serum MMP-1 was combined with CEA level or presence of vascular invasion, its prognostic implication was statistically significant (P=0.045 and P=0.015, respectively).
  
  
  CONCLUSIONS
  The tumor/stroma TIMP-1 intensity ratio in tissue is useful to predict tumor recurrence. Serum MMP-1 level showed a possibility as a prognostic biomarker.
authors.affiliation: Department of Medical Oncology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea.
authors.forename: Ho Jung
authors.initials: HJ
authors.lastname: An
authors.affiliation: Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chung-Ang University Hospital, Seoul, South Korea.
authors.forename: Soon Auck
authors.initials: SA
authors.lastname: Hong
authors.affiliation: Laboratory of Medical Oncology, Research Institutes of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jeong-Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Kyo Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Pulmonology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Young Kyoon
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Thoracic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jae Kil
authors.initials: JK
authors.lastname: Park
authors.affiliation: Department of Medical Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, South Korea. Electronic address: oncologykang@naver.com.
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism*
chemical_list: D002272:Carcinoembryonic Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1; D020781:Matrix Metalloproteinase 1
keywords: MMP-1; Non-small cell lung cancer; Prognosis; Ratio; TIMP-1