Abstract 3620: Histopathological associations with PTEN and ERG status in prostate biopsies from men treated with radiation

Abstract

Abstract Loss of the PTEN tumor suppressor gene in prostate cancer, which usually occurs by genomic deletion, is associated with adverse outcome. Recent work (PMID:23888040) suggested that PTEN activity is also required for maintaining genomic integrity and its loss may be associated with resistance to DNA damaging agents, such as ionizing radiation. We assembled a series of patients with intermediate to high grade clinically localized prostate cancer who underwent external beam radiation as their primary treatment. We obtained and regraded all positive biopsy cores according the the new Grade Grouping system for Gleason scores (PMID: 26492179) and performed analytically and clinically validated IHC assays for PTEN (associated with PTEN genomic alterations) and ERG (associated with the TMPRSS2-ERG gene fusion) on all positive tissue cores from a given biopsy that were contained in up to 5 separate FFPE blocks (n=589 positive cores, n positive cores ranged from 1 to 13, with median of 2 and mean of 3) from 193 patients. PTEN and ERG status were correlated with the new Grade Groups as well as other histopathological features, including the presence of cribriform architecture and intraductal carcinoma. Patients were 66% White, and 27% African American, and median age was 68.5. Grade Group designations (taken as the highest Grade group in the case) were as follows (Group 1 = 27%, Group 2 = 30%, Group 3= 15%, Group 4 = 18%, Group 5 = 11%). Overall there was at least some PTEN loss in 36% of cases. The presence of any PTEN loss in a given case was strongly associated with Grade Group (P<0.001, chi square), in that 17% of patients with Grade Group 1 showed any PTEN loss and 77% of patients with Grade Group 5 showed any PTEN loss. As seen in prior studies, PTEN loss was frequently heterogeneous in that only 11% of cases overall showed complete loss of PTEN in all tumor tissue examined. Homogeneous PTEN loss was also significantly associated with Grade Groups since 3.8% of cases of Grade Group 1 showed such loss and 27% of cases of Grade Group 5 showed such loss (P=0.024, chi square). PTEN loss was also associated with cribriform morphology (P<0.001) and the presence of intraductal carcinoma of the prostate (P<0.001), both known independent prognostic factors. Having any PTEN loss was also associated with ERG gene fusions since 22% of cases showed PTEN loss that were negative for ERG and 52% of cases showed PTEN loss in cases positive for ERG (P<0.000). As also previously found, the rate of PTEN loss was higher in samples from White patients than African Americans (complete PTEN loss = 3.9% in African Americans and 14% in White patients). The presence of any ERG positive tumor was also higher in tissues from White patients (54%) compared to African Americans (29%) (P=0.003). Additional analyses are underway regarding associations between PTEN and ERG status and outcomes after radiation therapy. Citation Format: Onur Ertunc, Mark Markowski, Phuoc T. Tran, Amol Narang, Jessica Hicks, Daniel Song, Jiayun Lu, Elizabeth A. Platz, Theodore Deweese, Angelo M. De Marzo. Histopathological associations with PTEN and ERG status in prostate biopsies from men treated with radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3620.