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Aims: To investigate the possibility of detecting small focal prostatic cancer by alpha-methylacyl CoA racemase (AMACR)/P504S immunohistochemistry on needle biopsy specimens that were previously interpreted as negative for carcinoma on routine haematoxylin and eosin (H&E)-stained sections., Methods: Prostate needle biopsy specimens (n = 793) previously interpreted as benign prostatic tissue by conventional morphology from 239 patients with prostatic cancer diagnosed in other biopsy cores taken at the same biopsy session were stained with the P504S monoclonal antibody. If a biopsy specimen stained positively, two pathologists independently reviewed the original corresponding H&E-stained sections to establish the malignant diagnosis., Results: Eighty-four of the 793 biopsy specimens showed AMACR immunoreactivity; nine of these (9/793, 1.1%) contained previously unrecognized small focal prostatic carcinoma (Gleason 6, N = 8; Gleason 8, N = 1). Six of nine (67%) carcinomas showed foamy/pseudohyperplastic (N = 3) or atrophic (N = 3) features. Additionally, five biopsy specimens (5/793, 0.6%) with positive AMACR staining that did not meet the criteria for prostatic cancer on the original H&E slides were considered to be atypia., Conclusions: In this study, we found a 1.1% false-negative rate for carcinoma on routine H&E-stained sections. AMACR immunohistochemical staining has shown the ability to improve detection of small focal prostatic carcinoma that could be missed by conventional histological examination.

Aim: Studies using a monoclonal (P504S) and a polyclonal antibody (p-AMACR) to alpha-methylacyl-CoA racemase (AMACR) have shown variable expression in prostate cancer (PCa). The goal is to compare the sensitivity of both antibodies in PCa and evaluate their utility in the work-up of atypical prostate needle biopsies (NBXs)., Methods and Results: A tissue microarray (TMA) with 248 samples of benign prostate, high-grade prostatic intraepithelial neoplasia (HGPIN) and PCa samples, 20 NBXs with minute PCa and 32 NBXs with 'atypical' foci were stained with P504S and p-AMACR. Ninety percent of PCa (76/76 TMA, 16/20 NBXs) showed predominantly strong p-AMACR expression while 87% (65/69 TMA, 16/20 NBXs) showed variable P504S expression (sensitivity 90% versus 87%, P = 0.10). In HGPIN, P504S and p-AMACR were positive in 77% and 91% of samples, respectively. In the 'atypical' NBXs group, 53% were classified as PCa, 12% benign and 35% atypical, suspicious for PCa, after review of the basal marker. Of atypical, suspicious for PCa, P504S/p-AMACR helped convert the diagnosis to PCa in 5/11 (45%) cases, where, despite negative basal cell markers, morphology was less than optimal., Conclusions: Differences between P504S and p-AMACR appear marginal and clinically insignificant. AMACR is negative in a subset of unequivocal minute PCa with both antibodies. However, when utilized in proper context, AMACR may offer significant advantage in converting an 'atypical' diagnosis to PCa where morphology and basal markers are less than optimal in resolving the diagnosis.