P0120 MMP11 overexpression: Poor prognosis in patients with urothelial carcinoma of the upper tract and urinary bladder.

Background: Through data mining from a published transcriptomic database of urinary bladder urothelial carcinomas (GSE32894), MMP11 was identified as the most significant gene showing stepwise upregulation among those associated with the regulation of metalloendopeptidase activity. We therefore analysed MMP11 protein expression and its association with clinicopathological factors and survival in our well-characterised cohort of urothelial cancers. Methods: Immunohistochemistry evaluated by using H-score was used to determine MMP11 protein expression in 295 urothelial carcinomas of the urinary bladder and 340 urothelial carcinomas of the upper urinary tract, 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. Findings: MMP11 protein overexpression was significantly associated with advanced pT status (upper urinary tract, p< 0.001; urinary bladder, p<0.001), nodal metastasis (upper urinary tract, p<0.001; urinary bladder, p=0.012), vascular invasion (upper urinary tract, p<0.001; urinary bladder, p<0.001), and perineural invasion (upper urinary tract, p=0.002; urinary bladder, p=0.006) in both groups of urothelial carcinomas. MMP11 overexpression not only predicted worse DSS (upper urinary tract, p<0.0001; urinary bladder, p<0.0001) and MeFS (upper urinary tract, p<0.0001; urinary bladder, p<0.0001) at univariate analysis, but also inferior DSS (upper urinary tract, p=0.005; urinary bladder, p=0.010) and MeFS (upper urinary tract, p=0.018; urinary bladder, p=0.026) in multivariate analysis. Interpretation: MMP11 overexpression is associated with more aggressive tumour phenotype and poor prognosis for patients with urothelial carcinomas of the upper urinary tract and urinary bladder, suggesting it may serve as a potential prognostic and a novel therapeutic target of urothelial carcinoma. [ABSTRACT FROM AUTHOR]