李威明1, 2, 3,4、吳文正1,4,5、李經家1,4,6、柯宏龍1,2,4、韋又菁7、葉信志1,4,6、
高雄醫學大學附設中和紀念醫院泌尿科1; 高雄醫學大學醫學研究所2; 衛生福利部屏東醫院3,; 高雄醫學大學醫學系泌尿科4; 高雄市立小港醫院泌尿科5高雄市立大同醫院泌尿科6; 高雄市立大同醫院病理科7;奇美醫學中心病理科8
The impact of MMP11 expression on the outcomes in patients with urothelial carcinoma
Wei-Ming Li 1,2,3,4, Wen-Jeng Wu 1,4,5, Ching-Chia Li 1,4,6, Hung-Lung Ke 1,2,4, Yu-Ching Wei 7,Hsin-Chin Yen1,4,6, Chien-Feng Li8, Chun-Nung Huang 1, 4, Chun-Hsiung Huang 1,4
1Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3 Pingtung Hospital, Ministry of Health and Welfare, Executive Yuan, Pingtung, Taiwan
4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5 Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
6 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
7 Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
8Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
Urothelial carcinoma (UC) is common in urinary bladder (UB) and upper urinary tract (UT). It represents a heterogeneous disease with high morbidity and mortality. Tumor invasion and progression are a multifactorial process promoted by microenvironmental changes that include overexpression of matrix metalloproteinases (MMPs). Through data mining from a published transcirptomic database of UBUCs (GSE32894), MMP11 was identified as the most significant gene showing stepwise upregulation among those associated with the regulation of metalloendopeptidase activity. We therefore analyze MMP11 protein expression and its association with clinicopathological factors and survivals in our well-characterized cohort of UC.
Materials and Methods:
Immunohistochemistry evaluated by using H-score was used to determine MMP11 protein expression in 295 UBUCs and 340 UTUCs, respectively. The medical records of these patients were reviewed retrospectively. The MMP11 expression status was further correlated with clinicopathological features as well as disease-specific survival (DSS) and metastasis-free survival (MeFS). Univariate and multivariate statistical analyses were performed to evaluate the prognostic predictors.
MMP11 protein overexpression was significantly associated with advanced pT status (UTUC, p<0.001; UBUC, p<0.001), nodal metastasis (UTUC, p<0.001; UBUC, p=0.012), vascular invasion (UTUC, p<0.001; UBUC, p<0.001) and perineural invasion (UTUC, p=0.002; UBUC, p=0.006) in both groups of UC. MMP11 overexpression not only predicted worse DSS (UTUC, p<0.0001; UBUC, p<0.0001) and MeFS (UTUC, p<0.0001; UBUC, p<0.0001) at univariate analysis, but implicated inferior DSS (UTUC, p=0.005; UBUC, p=0.010) and MeFS (UTUC, p=0.018; UBUC, p=0.026) in multivariate analysis.
MMP11 overexpression is associated with more aggressive tumor phenotype and poor prognosis for both patients with UTUC and UBUC, suggesting it may serve as a potential prognostic and a novel therapeutic target of UC.