Altered PCA3 and TMPRSS2-ERG expression in histologically benign regions of cancerous prostates: A systematic, quantitative mRNA analysis in five prostates

Abstract

Background: PCA3 and TMPRSS2-ERG are commonly overexpressed biomarkers in prostate cancer, but reports have emerged demonstrating altered expression also in areas outside the tumour foci in cancerous prostates. Our aim was to measure PCA3 and TMPRSS2-ERG expression systematically in all regions of prostate cross-sections, matching the data to corresponding tissue morphology. Methods: TMPRSS2-ERG and PCA3 mRNA levels were measured with quantitative reverse-transcription PCR assays in 270 samples from cross-sections of five radical prostatectomy specimens. ERG expression was examined by immunohistochemistry. Results: TMPRSS2-ERG mRNAs were detected in three patients and in 15 tissue samples in total. These included two carcinoma samples and 13 histologically benign samples, eight of which were located next to malignant tumours or PIN (prostatic intraepithelial neoplasia) lesions and five of which did not reside in the vicinity of any evident carcinoma foci. ERG protein expression was limited to areas of TMPRSS2-ERG mRNA expression, but did not identify all of them. PCA3 expression was detected in all five cross-sections, with statistically significant, three-fold higher expression in carcinoma regions. Conclusions: TMPRSS2-ERG expression was detected in carcinoma foci, regions next to them, and in samples not adjacent to carcinoma foci. Claimed as a cancer-associated phenomenon, this fusion gene measurement could, if validated with a larger cohort, be utilized as an addition to histological analysis to predict current or future cancer risk in men with negative biopsies. Molecular changes outside the carcinoma foci are also indicated for PCA3, as its expression was only moderately increased in the carcinoma regions.