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

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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.

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