Revisiting the immunophenotype of nephrogenic adenoma

Nephrogenic adenoma (NA) is a rare benign lesion of the urinary tract. Although its histogenesis is still debated, several reports suggest that the lesion has a renal tubular cell origin or differentiation. As NA can be difficult to distinguish from malignant conditions such as prostate cancer, there is a need for reliable markers. Unfortunately, it has been reported that NA cells also stained positive for the prostate cancer marker alpha-methylacyl-coenzyme A racemase (AMACR). Because all the previous studies have used an avidin-biotin (AB) detection procedure, and because cells with tubular renal differentiation are likely to contain a high level of endogenous biotin, we investigated in NA the expression of several markers including AMACR, using both AB and biotin-free detection systems. We assessed the expression of p63, cytokeratins 7 and 20, CD10 (proximal tubule marker), MUC1 (distal tubule marker), PAX2, and AMACR on 14 NAs (from 6 patients) grouped on a tissue microarray. The tissue microarray also included renal, urothelial, and prostate tissues. Staining was detected using both AB and biotin-free Envision systems. Detection with the AB procedure leads to nonspecific staining in kidney samples and NA. More specific expression was obtained by using the Envision kit, and only CK7, PAX2, and MUC1 remained positive in NA, without any AMACR staining. These findings provide supporting evidence that NA has the differentiation of distal renal tubules, and strongly suggest that AMACR, when detected with a biotin-free procedure, can be used as a reliable marker for distinguishing NA from prostate cancer.