GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States

Abstract

GSTP1 is a member of the Glutathione-S-transferase (GST) family silenced by CpG island DNA hypermethylation in 90–95% of prostate cancers. However, prostate cancers expressing GSTP1 have not been well characterized. We used immunohistochemistry against GSTP1 to examine 1673 primary prostatic adenocarcinomas on tissue microarrays (TMAs) with redundant sampling from the index tumor from prostatectomies. GSTP1 protein was positive in at least one TMA core in 7.7% of cases and in all TMA cores in 4.4% of cases. The percentage of adenocarcinomas from Black patients who had any GSTP1 positive TMA cores was 14.9%, which was 2.5 times higher than the percentage from White patients (5.9%; P < 0.001). Further, the percentages of tumors from Black patients who had all TMA spots positive for GSTP1 (9.5%) was 3-fold higher than the percentage from White patients (3.2%; P<0.001). In terms of association with other molecular alterations, GSTP1 positivity was enriched in ERG positive cancers among Black men. By in situ hybridization, GSTP1 mRNA expression was concordant with protein staining, supporting the lack of silencing of at least some GSTP1 alleles in GSTP1-positive tumor cells. This is the first report revealing that GSTP1-positive prostate cancers are substantially over-represented among prostate cancers from Black compared to White men. This observation should prompt additional studies to determine whether GSTP1 positive cases represent a distinct molecular subtype of prostate cancer and whether GSTP1 expression could provide a biological underpinning for the observed disparate outcomes for Black men.

Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth

“…Scale bar is 100 µm. E Immunohistochemistry analysis of GALNT7 protein in a previously published TMA containing matched tumour and normal tissue from the same patient [79]. GALNT7 protein is significantly increased in prostate tumour tissue relative to matched normal tissue from the same patient (n = 200, paired t test, p < 0.001).…”

Presence of cells in the polyaneuploid cancer cell (PACC) state predicts the risk of recurrence in prostate cancer

“…Case–cohort was originally assembled to include as “cases” men with metastasis or with biochemical recurrence (BCR) with a rapid PSA doubling time (<10 months) and who were also considered to be at high risk of metastasis. 42 From the cohort of 2159 patients, a subcohort of 244 patients was selected, and 115 cases (73 with BCR and rapid PSA doubling time, and 42 with metastasis). Tissue samples from these men were analyzed for PACC; samples from 307 men were informative for PACC.…”

Modeling Human Prostate Cancer Metastasis in Mice via Resection of Subcutaneous Allografts

“…H&E staining was completed by the Johns Hopkins University Oncology Tissue Services Core. Immunohistochemistry (IHC) was performed using a Ventana DISCOVERY ULTRA Autostainer using the DISCOVERY anti-HQ HRP kit as previously described ( 8 ). We validated an automated assay against androgen receptor (AR) using a monoclonal antibody (Cat.…”