title: Significant relationship of matrix metalloproteinase 9 with nuclear grade and prognostic impact of tissue inhibitor of metalloproteinase 2 for incidental clear cell renal cell carcinoma.
abstract: OBJECTIVE
  To examine the immunoreactivity of tumors for matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1, TIMP-2), and membrane type MMP 1 (MT-MMP-1), to evaluate the optimum assessment of incidental renal cell carcinoma.
  
  
  METHODS
  Tumor samples from 120 incidental clear cell renal cell carcinoma (ICRCC) patients without distant metastasis or invasion beyond Gerota's fascia were obtained by surgery. They were immunohistochemically stained for MMP-2, MMP-9, TIMP-1, TIMP-2, and MT-MMP-1. Immunoreactivity for these factors was analyzed by semiquantitative multivariate analysis for cancer-specific survival.
  
  
  RESULTS
  The cancer-specific 5 and 10-year survival rates were 91.4% and 91.4%, respectively. Univariate analysis revealed that nuclear grade (P = 0.0064) and TIMP-2 (P = 0.034) were significant prognostic factors. Matrix metalloproteinase 9 has a significant relationship with high nuclear grade RCC (P = 0.017) and was found to be an independent prognosticator by Cox multiple regression analysis (P = 0.0028).
  
  
  CONCLUSIONS
  Nuclear grade and TIMP-2 were significant prognostic factors of ICRCC. Multivariate analysis showed that a nuclear grade greater than 3 was associated with a 566% significant increase in the odds of cancer death. Strong expression of MMP-9 was associated with a 774% increase in the odds of high nuclear grade, with statistical significance. Although ICRCC is well known for having a favorable prognosis, patients with tumors having a high nuclear grade and strongly expressed MMP-9 and TIMP-2 should undergo strict postoperative follow-up.
authors.affiliation: Department of Urology, Nihon University School of Medicine, Tokyo, Japan. asahigen@med.nihon-u.ac.jp
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kawata
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nagane
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirakata
authors.forename: Taketo
authors.initials: T
authors.lastname: Ichinose
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okada
authors.forename: Kenya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14