Global expression of AMACR transcripts predicts risk for prostate cancer – a systematic comparison of AMACR protein and mRNA expression in cancerous and noncancerous prostate

BACKGROUND The high false negative rates for initial prostate biopsies refer a large number of the men for repeat biopsies each year. Therefore, biomarkers associated with high risk of the presence of malignancy in histologically benign biopsies could provide a tool to discriminate the patients who need repeat biopsy or intensive follow-up from those who do not. Here we examined the diagnostic applicability of alpha-methylacyl CoA racemase (AMACR) and androgen receptor (AR) mRNA expression and AMACR protein levels in benign and cancerous prostatic tissue. METHODS AMACR and AR mRNA levels were measured with quantitative, reverse-transcription PCR (qRT-PCR) assays in 79 radical prostatectomy (RP) cases (including 69 benign (RP-Be) and 69 cancerous (RP-PCa) samples) and 19 benign prostate samples obtained from cystoprostatectomies. To further determine the detailed areas of altered AMACR expression, AMACR mRNA level measurement and protein staining were performed for three cross-sectioned RP cases. RESULTS The median AMACR and AR expression levels were 194.6 (p < 0.0001) and 6.6 (p = 0.0004) times higher in RP-PCa samples than in the benign cystoprostatectomy (CP) samples, respectively. There was no statistically significant difference between RP-PCa and RP-Be samples, except for AMACR/KLK3 (Kallikrein-Related Peptidase 3) ratio, which was significantly higher in RP-PCa samples than in RP-Be samples (p = 0.016). In the systematic study of cross-sections, AMACR mRNA was detected in all of the studied areas including histologically benign tissue, but at significantly higher levels in carcinoma areas (p < 0.001). AMACR protein expression was detected in 80 % (28/35) of the areas that contained carcinoma and in 37 % (44/119) of the benign and PIN areas from the same patients. CONCLUSIONS AMACR transcripts were detected in all RP-PCa and RP-Be samples but not in non-cancerous CP samples, which suggest a global increase of AMACR expression in cancerous prostates. Therefore patients with false negative biopsies might benefit from an AMACR mRNA measurement when assessing their cancer risk.