Wei-Ming Li1,2,3,4, Yu-Ching Wei5, Chun-Nung Huang2,3, Hung-Lung Ke2,3, Ching-Chia Li1,2,3,6, Hsin-Chih Yeh1,2,3,5, Lin-Li Chang1,7, Chun-Hsiung Huang1,2,3, Chien-Feng Li8,9,10,11,12, Wen-Jeng Wu1,2,3,6,13,14. 1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 3. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan. 5. Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. 6. Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. 7. Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 8. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan. 9. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan. 10. National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan. 11. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 12. Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 13. Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. 14. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
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;113:700-707.
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;113:700-707.
Authors: Aurélie Mbeutcha; Romain Mathieu; Morgan Rouprêt; Kilian M Gust; Alberto Briganti; Pierre I Karakiewicz; Shahrokh F Shariat Journal: Transl Androl Urol Date: 2016-10
Authors: Ricardo L Favaretto; Stênio C Zequi; Renato A R Oliveira; Thiago Santana; Walter H Costa; Isabela W Cunha; Gustavo C Guimarães Journal: Int Braz J Urol Date: 2018 Jan-Feb Impact factor: 1.541