title: Matrix metalloproteinase-11 as a marker of metastasis and predictor of poor survival in urothelial carcinomas.
abstract: OBJECTIVE
  Urothelial carcinomas (UC) of urinary bladder (UB) and upper urinary tract (UT) are heterogeneous diseases with high morbidity and mortality. We looked for genes with metalloendopeptidase activity in a published UBUC transcriptomic database (GSE31684):MMP-11 was the most significant, showing stepwise up-regulation. We analyzed MMP-11 expression and association with clinicopathologic factors and survival in our well-characterized cohort of UCs.
  
  
  METHODS
  We determined MMP-11 expression in 295 UBUCs and 340 UTUCs with immunohistochemistry, evaluated by H-score. In a retrospective study, MMP-11 expression was correlated with clinicopathologic features and with disease-specific survival (DSS) and metastasis-free survival (MeFS). The statistical significance was evaluated with univariate and multivariate analyses.
  
  
  RESULTS
  High MMP-11 expression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular and perineural invasion, and frequent mitoses. In multivariate Cox regression analyses, which adjusted for standard clinicopathologic characteristics, MMP-11 expression was independently associated with cancer-specific mortality (hazard ratio [HR] in UTUC:3.027, P = 0.005; in UBUC: 2.631, P = 0.010) and with metastasis development (HR in UTUC:2.261, P = 0.018; in UBUC:1.801, P = 0.026).
  
  
  CONCLUSIONS
  MMP-11 overexpression is associated with aggressive tumor phenotype and unfavorable clinical outcome in UTUC and UBUC, suggesting it may serve as a novel prognostic and therapeutic target. J. Surg. Oncol. 2016;113:700-707. © 2016 Wiley Periodicals, Inc.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan.
authors: Wei-Ming
authors: WM
authors: Li
authors: Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Yu-Ching
authors: YC
authors: Wei
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chun-Nung
authors: CN
authors: Huang
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Hung-Lung
authors: HL
authors: Ke
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Ching-Chia
authors: CC
authors: Li
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Hsin-Chih
authors: HC
authors: Yeh
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Lin-Li
authors: LL
authors: Chang
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chun-Hsiung
authors: CH
authors: Huang
authors: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.|Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.|National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan.|Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chien-Feng
authors: CF
authors: Li
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Wen-Jeng
authors: WJ
authors: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053507:Matrix Metalloproteinase 11 / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C511771:MMP11 protein, human; D053507:Matrix Metalloproteinase 11
keywords: MMP-11; bladder cancer; prognosis; upper urinary tract urothelial carcinoma; urothelial carcinoma