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 (GSTS) 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 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). The increased percentage of GSTP1 positive cases in Black men was present only in ERG positive cases. 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 the GSTP1-positive prostate cancer subset is 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.

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

“…The 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) who were also considered to be at high risk of metastasis 41 . 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).…”

“…A total of 2807 tissue samples of matched normal/benign and cancer were arrayed in 9 TMA blocks. These TMAs were all constructed as described [41][42][43][44] from the index tumor (highest grade) with a 3-4 fold sampling redundancy. On H&E stained tissue sections and TMA sections, identifying PACCs is difficult since they often have indistinct cell membranes therefore making it difficult to distinguish "pseudo" multinucleation from the real ones.…”

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.…”

“…A total of 2807 tissue samples of matched normal/benign and cancer were arrayed in nine TMA blocks. These TMAs were all constructed as described [42][43][44][45] from the index tumor (highest grade) with a 3-4-fold sampling redundancy. On hematoxylin and eosin (H&E)-stained tissue sections and TMA sections, identifying PACCs is difficult since they often have indistinct cell membranes, thus making it difficult to distinguish "pseudo" multinucleation from the real ones.…”