Abstract 5303: GSTP1 positive prostate cancer

Abstract

Abstract Introduction: GSTP1 is a member of the Glutathione-S-transferase family, known to be silenced by CpG island DNA methylation in approximately 90% of prostatic adenocarcinomas. However, the cases that are not densely methylated have not been extensively characterized in terms GSTP1 expression or clinico-pathological features. Description of experimental procedures: We analytically validated an automated IHC assay against human GSTP1 using well-known cell line controls and human prostate cancer tissues. We examined 33 TMAs from 1296 prostatectomy patients using the index tumor with 4-fold redundancy from patients from 1993 to 2015. TMA slides stained for GSTP1 were scanned and uploaded to a web based image scoring platform (TMAJ). The images were reviewed by two different pathologists with expertise in prostate cancer. The scoring system followed a two-tiered approach, noted as positive (carcinomas with any nuclear and/or cytoplasmic staining), and as negative (carcinoma cells with no nuclear or cytoplasmic stain) in the presence of benign stromal or inflammatory cells that served as internal controls. The GSTP1 positive staining was correlated with Gleason grade groups, pathological stage, and age. Results: After exclusion for inadequate tissue staining, GSTP1 was evaluated in 4326 TMA cores with carcinoma. GSTP1 IHC staining was positive in 190 cores (4.3%), corresponding to 75 patients (5.9% of patients had GSTP1 positive cancer). Of these 190 positive cores, 109 showed homogeneous (100% positive) tumor cell staining while 81 showed heterogeneous staining, with mixed positive and negative regions. In 43 patients (3.3%), all TMA cores containing carcinoma stained positively. In a number of standard slides from prostatectomies, GSTP1 positive IHC staining cases were also found to be positive for GSTP1 mRNA by in situ hybridization. There was no correlation between GSTP1 positive staining, Gleason grade group, pathological stage, margin status or patient age. Preliminary analysis in a subset of cases showed no correlation with TMPRSS2-ERG status or PTEN loss. Conclusion: GSTP1 protein is present in approximately 5.9% of clinically localized prostate cancers and in approximately 50% of these positive cases, all TMA cores with carcinoma stained positively. Citation Format: Igor D. Vidal, Stephanie Glavaris, Tracy Jones, Jessica Hicks, Bruce J. Trock, Srinivasan Yegnasubramanian, William Nelson, Angelo M. De Marzo. GSTP1 positive prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5303.