Abstract A029: Patterns of ERG and GR protein expression in localized prostate cancer

Abstract Background: ERG is a member of the ETS-family of transcription factors, and in prostate cancer its overexpression is typically driven by the TMPRSS2-ERG fusion, which places ERG under androgen receptor (AR) regulated expression of TMPRSS2. ETS fusion protein expression occurs in almost 50% of prostate adenocarcinomas. Glucocorticoid receptor (GR) is a nuclear steroid hormone receptor that binds glucocorticoids and regulates gene transcription. When AR activity is blocked by androgen deprivation therapy (ADT), GR expression may increase and substitute for AR in driving certain transcriptional programs. Recent studies suggest that AR activation can modulate GR chromatin binding and patients with higher co-expression of AR and GR had better outcomes compared to high AR/low GR. While the prognostic relationship of ERG rearrangements has been analyzed in many of studies, ERG cannot be used as a single marker for the prognosis of aggressive prostate cancer phenotypes. We sought to establish whether there was a tendency towards a co-occurrence or mutual exclusivity between ERG and GR. Methods: We performed immunohistochemistry for a cohort of treatment-naïve radical prostatectomies (n=62) from patients with localized intermediate and high-risk prostate cancer. We analyzed entire slides to measure the frequency of concordance for ERG and GR. We performed a one-sided Fisher’s exact test. Results: 25/62 cases (40%) harbored tumor cells that were ERG-positive, of which 18 demonstrated intratumoral heterogeneity. 59/62 cases (95%) harbored tumor cells that were GR-positive, of which 57 demonstrated intratumoral heterogeneity. Examination of individual tumor foci revealed that in 39/62 cases (63%) the majority of tumors cells each slide were concordant for ERG and GR. The result of one-sided Fisher’s exact test showed significant co-occurrence of ERG and GR expression (P < 0.001). Mutual exclusivity was not favored. Conclusion: Although there is no known direct relationship between ERG and GR, our data indicates that the growth of prostate cancer cells and their survival under untreated conditions favors the co-occurrence or co-absence of ERG and GR. Further studies are needed to clarify the mechanistic basis underlying an association between ERG and GR expression. Citation Format: Sumeyra Kartal, Shana Trostel, Adam Sowalsky. Patterns of ERG and GR protein expression in localized prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A029.