T2E (TMPRSS2-ERG) fusion transcripts are associated with higher levels of AMACR mRNA and a subsequent prostate cancer diagnosis in patients with atypical small acinar proliferation

Abstract

Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 (TMPRSS2) and genes from the ETS transcription factor family, most commonly ERG and ETV1, result in alteration that responsible for oncogenic activity in prostate cancer (PC). The aims of the present study were to: 1) investigate the frequency of these fusion transcripts in prostate tissue samples obtained from patients diagnosed with atypical small acinar proliferation (ASAP), 2) determine any clinical significance of T2E expression at the RNA level in predicting PC detection in subsequent biopsies, and 3) evaluate expression of the PC marker, alpha-methylacyl-CoA racemase (AMACR), according to T2E status by real-time quantitative reverse transcription PCR (RT-qPCR). T2E transcripts were detected in 31.7% (n = 20) of the patients examined, and this was significantly associated with subsequent detection of PC in ASAP patients with a prostate specific antigen (PSA) level of 4-10 ng/ml (p = 0.045). AMACR expression was also significantly higher in the patients who were diagnosed with PC in subsequent biopsies than in the patients who were not diagnosed with PC (p = 0.034) and in T2E-positive ASAP patients (p = 0.002) compared to T2E-negative ASAP patients. Although these results need to be further clinically validated, we suggest that the presence of T2E transcript, in association with higher AMACR expression, is an indicator of PC risk from a T2E-positive focus or an unsampled malignant gland adjacent to a T2E-positive site in ASAP lesions.