Prognostic value of alpha-methyl CoA racemase (AMACR) expression in renal cell carcinoma

Alpha-methyl CoA racemase (AMACR) is used as an immunohistochemical marker for renal cell carcinoma (RCC) subtyping to distinguish papillary (pap) RCC. Expression of AMACR in other renal tumor subtypes is inhomogeneous, and the clinical and prognostic value of AMACR is unknown. The aim of this study was to asses AMACR protein expression in different RCC subtypes and to investigate its prognostic significance.

Protein expression of AMACR was analyzed in 1,088 renal tumor samples, among them 809 clear cell RCC and 151 papRCC, by immunohistochemistry using tissue microarry (TMA) technique. Results were correlated with clinicopathological data and to follow-up data [overall (OS)/cancer-specific survival (CSS)].

Frequency of AMACR expression was significantly higher in papRCC compared to other tumor subtypes (83% vs. 15-35%, p < 0.0001). Presence of AMACR did not correlate with stage or nodal metastases in papRCC. In a dichotomized scoring (negative vs. positive expression), an inverse correlation between higher grade (p = 0.03) and presence of distant metastasis (p = 0.014) was observed in papRCC. AMACR expression correlated with the presence of nodal metastasis in ccRCC (p = 0.02). Both in ccRCC and in papRCC, OS and CSS did not correlate with the AMACR expression status.

The high expression in papRCC confirms AMACR to be a marker for subtype differentiation in RCC, while a missing expression in this subtype seems to be associated with negative pathological features. However, in contrast to other tumor entities, AMACR expression seems to have a limited prognostic impact in renal carcinoma, especially with regard to survival.