Is atypical adenomatous hyperplasia of the prostate a precursor lesion?

Abstract

Alpha-methylacyl-CoA racemase (AMACR) is highly expressed in prostatic adenocarcinoma. The precursor nature of atypical adenomatous hyperplasia (AAH) is uncertain. One hundred twenty-one AAH foci from 101 patients who underwent transurethral prostatic resection or prostatectomy were immunohistochemically analyzed for AMACR, high molecular weight cytokeratin 34βE12, and p63 expression by a triple antibody (PIN4) cocktail stain. Sixty-eight foci (56%) of AAH showed no AMACR immunostaining. Fourteen cases (12%) showed weak AMACR immunoreactivity in 1-9% of lesional cells. Sixteen cases (13%) showed strong immunopositivity for AMACR in >50% of lesional cells. AMACR expression in AAH was significantly higher in cases in which coexisting PCA was present, compared with its expression in AAH foci without coexisting PCA (P = 0.03). Strong diffuse AMACR positivity in over 50% of lesional cells was seen almost exclusively in AAH foci with coexisting PCA (P = 0.002). AMACR expression in AAH showed no correlation with patient age (P = 0.38), specimen type (P = 0.35), prostate weight (P = 0.80), zonal location (P = 0.50), distance to cancer (P = 0.28), Gleason score (P = 0.06), or pathologic stage (P = 0.23). Increased AMACR expression showed a negative correlation with the size of AAH foci (P = 0.03). All AAH lesions showed fragmented basal cell layers, highlighted by p63 and high molecular weight cytokeratin staining. A significant percentage of AAH cases show stronger and more extensive AMACR expression when associated with prostatic adenocarcinoma, as compared to AAH foci found without coexisting prostate cancer. Our data provide additional evidence linking AAH to prostatic adenocarcinoma.