BACKGROUND AND OBJECTIVES - 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 Wiley Periodicals, Inc.
Journal of surgical oncology. 2016 Feb 10 [Epub ahead of print]
Wei-Ming Li, Yu-Ching Wei, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Hsin-Chih Yeh, Lin-Li Chang, Chun-Hsiung Huang, Chien-Feng Li, Wen-Jeng Wu
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan., Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan., Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.