P0093 AMACR overexpression is associated with clinical and biological aggressiveness in urothelial carcinomas of the upper urinary tract and urinary bladder

Abstract

Background Alpha-methylacyl CoA racemase (AMACR) is essential for catabolism of branched-chain fatty acids, allowing their subsequent β -oxidation to generate energy. However, its significance has not been assessed in urothelial carcinoma. We therefore analysed the clinicopathological and biological significance of AMACR expression in urothelial carcinoma. Methods Laser capture microdissection coupled with real-time qRT-PCR was used to detect AMACR transcript level in 22 urothelial carcinomas of the urinary bladder. Immunohistochemistry evaluated by using H-score was used to determine AMACR protein expression in 295 urothelial carcinomas of the urinary bladder and 340 urothelial carcinomas of the upper urinary tract. mRNA and protein expression were correlated with clinicopathological features. AMACR protein expression was further evaluated for associations with disease-specific survival (DSS) and metastasis-free survival (MeFS). In vitro, AMACR overexpressing urothelial carcinoma cell lines (BFTC905 and RTCC-1) were evaluated for its biological function using RNA interference. Findings Increments of AMACR transcript level was associated with higher pT status ( p = 0.017). AMACR protein overexpression was significantly associated with advanced pT status (both p p ⩽ 0.001), high histological grade (both p ⩽ 0.001), vascular invasion (urothelial carcinomas of the upper urinary tract, p p = 0.003), frequent mitoses (urothelial carcinomas of the upper urinary tract, p = 0.007; urothelial carcinomas of the urinary bladder, p p = 0.025; urothelial carcinomas of the urinary bladder, p = 0.001) and MeFS (urothelial carcinomas of the upper urinary tract, p = 0.028; urothelial carcinomas of the urinary bladder, p = 0.019) in multivariate analysis. In both urothelial carcinoma cell lines, stable AMACR knockdown resulted in impaired cell proliferation, as well as migration/invasion capabilities. Interpretation AMACR overexpression is associated with advanced clinical features for patients with urothelial carcinoma and may serve as a potential prognostic biomarker and a novel therapeutic target.