title: Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression.
abstract: Alpha-methylacyl-CoA racemase (AMACR/P504S) is a useful biomarker of prostate cancer. We evaluated the expression of AMACR in upper urinary tract urothelial carcinomas with respect to associations with tumour stage, grade and metastasis-free survival. A total of 268 tumours were investigated immunohistochemically using a tissue microarray technique. AMACR expression was noted in 127 of 261 (48.7%) evaluated tumours and was associated with high tumour stage [58 of 139 (41.7%) pTa/pT1 vs. 69 of 122 (56.6%) pT2-pT4, P=0.019] and high tumour grade [44 of 137 (32.1%) low vs. 83 of 124 (66.9%) high grade, P<0.001]. In addition, AMACR expression was associated with the presence of tumour necrosis (P<0.001) and marked stromal desmoplasia (P=0.0026). This correlation indicates that increased AMACR expression might be related to hypoxia-induced changes in cancer cell metabolism, such as increased dependence on fatty acid oxidation for energy generation. Progressive disease was observed in 73 of 183 (39.9%) patients with solitary invasive carcinomas and was associated with AMACR expression (P=0.017). Multivariate analysis, however, proved only pT-stage >1 (P<0.001) and high tumour grade (P<0.001) to be independent predictors of patient outcome. In conclusion, AMACR expression correlated with advanced tumour stage and grade and may serve as an additional prognostic indicator in upper urinary tract urothelial cancer.
authors.affiliation: Institute of Pathology, Medical University Graz, Auenbruggerplatz 25, Graz, Austria. cord.langner@meduni-graz.at
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.forename: Gerhild
authors.initials: G
authors.lastname: Rupar
authors.forename: Sebastian
authors.initials: S
authors.lastname: Leibl
authors.forename: Georg
authors.initials: G
authors.lastname: Hutterer
authors.forename: Thomas
authors.initials: T
authors.lastname: Chromecki
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.forename: Peter
authors.initials: P
authors.lastname: Rehak
authors.forename: Richard
authors.initials: R
authors.lastname: Zigeuner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D019998:Racemases and Epimerases / Q000378:metabolism*; D015996:Survival Rate; D014516:Ureteral Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase