TMPRSS2: ERG expression in prostate cancer—Imaging and clinicopathological correlations.

Abstract

284 Background: The TMPRSS2:ERG gene fusion (T:E) is found in up to 70% of prostate cancers (PCa) and results in androgen dependent overexpression of ERG, promoting tumor growth. The early identification of T:E may be helpful even in low-risk PCa. Although T:E can be non-invasively detected in urine, its correlation with new imaging tools (MRI and high-frequency ultrasound) and clinical outcome remains vague.This study investigates T:E expression in patients scheduled for random/software-assisted MRI or micro-ultrasound (29Mhz) fusion biopsy. Methods: This is a prospective cohort study in patients with suspected PCa enrolled between 2016 and 2019, approved by local authorities with Prot. N. 336/19, 14/05/2019. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they had ³1 suspicious lesion (PI-RADS V.2 >2) at mpMRI or PRIMUS >2 at MICRO-US. For each patient, 1 prostatic core from the highest PI-RADS or PRIMUS lesion was collected for T:E analysis (a core from the right lobe in negative patients). Histological analyses were performed by experienced genitourinary pathologists. RNA was extracted from a dedicated fresh biopsy and RT-PCR was performed with different primer couples to detect the most frequent T:E fusions. All amplified products were checked by sequencing. Results: The cohort consists of 92 patients (median PSA 7.13 ng/ml, IQR 5.25-11.04 - average age 65ys), 81 with a diagnosis of PCa after biopsy. mpMRI was performed on 63 (68.5%) patients and was positive in 58 (92%), who underwent fusion biopsy. T:E fusion transcripts were detected in 23.5% of individuals with a diagnosis of PCa. Among patients positive for T:E, those analyzed by MRI were 100% positive (73% PI-RADS ≥4), those analyzed by MICRO-US were 83% positive. Sensitivity of the T:E assay for any PCa was 23.5%, specificity 100%, with negative and positive predicting values of 15% and 100%. There was no correlation between T:E and family history, PSA, PIRADS, PRI-MUS and Gleason score. Conclusions: Our finding showed a 100% of specificity making T:E an attractive tool for early cancer detection. In the future, identification of T:E in semen could represent a screening test for clinical stratification of patients with suspected PCa.