Comparison of Pathologist and Artificial Intelligence-based Grading for Prediction of Metastatic Outcomes After Radical Prostatectomy.

Gleason grade group (GG) is the most powerful prognostic variable in localized prostate cancer; however, interobserver variability remains a challenge. Artificial intelligence algorithms applied to histopathologic images standardize grading, but most have been tested only for agreement with pathologist GG, without assessment of performance with respect to oncologic outcomes. We compared deep learning-based and pathologist-based GGs for an association with metastatic outcome in three surgical cohorts comprising 777 unique patients. A digitized whole slide image of the representative hematoxylin and eosin-stained slide of the dominant tumor nodule was assigned a GG by an artificial intelligence-based grading algorithm and was compared with the GG assigned by a contemporary pathologist or the original pathologist-assigned GG for the entire prostatectomy. Harrell's C-indices based on Cox models for time to metastasis were compared. In a combined analysis of all cohorts, the C-index for the artificial intelligence-assigned GG was 0.77 (95% confidence interval [CI]: 0.73-0.81), compared with 0.77 (95% CI: 0.73-0.81) for the pathologist-assigned GG. By comparison, the original pathologist-assigned GG for the entire case had a C-index of 0.78 (95% CI: 0.73-0.82). PATIENT SUMMARY: Artificial intelligence-enabled prostate cancer grading on a single slide was comparable with pathologist grading for predicting metastatic outcome in men treated by radical prostatectomy, enabling equal access to expert grading in lower resource settings.

Medical Imagery: Cytomegalovirus sialadenitis in a patient with B-cell acute lymphoblastic leukemia.

Cytomegalovirus (CMV) can cause a broad range of diseases, with severity depending on immune status, comorbidities, and age. Initial CMV infection usually occurs in childhood and is typically asymptomatic, leading to lifelong latency. In immunocompromised patients, CMV can affect multiple organs, but salivary gland infections are rare. This study presents a case of a 66-year-old woman with B-cell acute lymphoblastic leukemia who developed swelling and pain in the right preauricular region during pre-transplant consolidation therapy. Despite a recent bone marrow biopsy indicating morphological remission and a flow cytometry analysis detecting only 0.04 % B lymphoblasts, she exhibited these symptoms. A CT scan revealed enlargement, hyperdensity, and enhancement of the right parotid glands, with accompanying subcutaneous edema. A biopsy of the right parotid gland showed a dense interstitial lymphoplasmacytic infiltrate with numerous Cowdry bodies and smaller granular cytoplasmic inclusions, all testing positive for CMV immunohistochemistry. The findings confirm the diagnosis of CMV sialadenitis in an immunocompromised patient. This case underscores the importance of considering CMV infections in similar clinical scenarios, particularly in patients with compromised immune systems.

Predicting Prostate Cancer Molecular Subtype With Deep Learning on Histopathologic Images.

Microscopic examination of prostate cancer has failed to reveal a reproducible association between molecular and morphologic features. However, deep-learning algorithms trained on hematoxylin and eosin (H&E)-stained whole slide images (WSI) may outperform the human eye and help to screen for clinically-relevant genomic alterations. We created deep-learning algorithms to identify prostate tumors with underlying ETS-related gene (ERG) fusions or PTEN deletions using the following 4 stages: (1) automated tumor identification, (2) feature representation learning, (3) classification, and (4) explainability map generation. A novel transformer-based hierarchical architecture was trained on a single representative WSI of the dominant tumor nodule from a radical prostatectomy (RP) cohort with known ERG/PTEN status (n = 224 and n = 205, respectively). Two distinct vision transformer-based networks were used for feature extraction, and a distinct transformer-based model was used for classification. The ERG algorithm performance was validated across 3 RP cohorts, including 64 WSI from the pretraining cohort (AUC, 0.91) and 248 and 375 WSI from 2 independent RP cohorts (AUC, 0.86 and 0.89, respectively). In addition, we tested the ERG algorithm performance in 2 needle biopsy cohorts comprised of 179 and 148 WSI (AUC, 0.78 and 0.80, respectively). Focusing on cases with homogeneous (clonal) PTEN status, PTEN algorithm performance was assessed using 50 WSI reserved from the pretraining cohort (AUC, 0.81), 201 and 337 WSI from 2 independent RP cohorts (AUC, 0.72 and 0.80, respectively), and 151 WSI from a needle biopsy cohort (AUC, 0.75). For explainability, the PTEN algorithm was also applied to 19 WSI with heterogeneous (subclonal) PTEN loss, where the percentage tumor area with predicted PTEN loss correlated with that based on immunohistochemistry (r = 0.58, P = .0097). These deep-learning algorithms to predict ERG/PTEN status prove that H&E images can be used to screen for underlying genomic alterations in prostate cancer.

Contemporary Management Before Chronic Total Occlusion Percutaneous Coronary Interventions: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

BACKGROUND: Guidelines recommend maximal antianginal medical therapy before attempted coronary artery chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The degree to which this occurs in contemporary practice is unknown. We aimed to characterize the frequency and variability of preprocedural use of antianginal therapy and stress testing within 3 months before PCI of CTO (CTO PCI) across a nationally integrated health care system. METHODS: We identified patients who underwent attempted CTO PCI from January 2012 to September 2018 within the Veterans Affairs Healthcare System. Patients were categorized by management before CTO PCI: presence of ≥2 antianginals, stress testing, and ≥2 antianginals and stress testing within 3 months of PCI attempt. Multivariable logistic regression and inverse propensity weighting were used for adjustment before trimming, with median odds ratios calculated for variability estimates. RESULTS: Among 4250 patients undergoing attempted CTO PCI, 40% received ≥2 antianginal medications and 24% underwent preprocedural stress testing. The odds of antianginal therapy with more than one medication before CTO PCI did not change over the years of the study (odds ratio [OR], 1.0 [95% CI, 0.97-1.04]), whereas the odds of undergoing preprocedural stress testing decreased (OR, 0.97 [95% CI, 0.93-0.99]), and the odds of antianginal therapy with ≥2 antianginals and stress testing did not change (OR, 0.98 [95% CI, 0.93-1.04]). Median odds ratios (MOR) showed substantial variability in antianginal therapy across hospital sites (MOR, 1.3 [95% CI, 1.26-1.42]) and operators (MOR, 1.35 [95% CI, 1.26-1.63]). Similarly, preprocedural stress testing varied significantly by site (MOR, 1.68 [95% CI, 1.58-1.81]) and operator (MOR, 1.80 [95% CI, 1.56-2.38]). CONCLUSIONS: Just under half of patients received guideline-recommended management before CTO PCI, with significant site and operator variability. These findings suggest an opportunity to reduce variability in management before CTO PCI.

Association of Residual Ischemic Disease With Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: Anatomical scoring systems have been used to assess completeness of revascularization but are challenging to apply to large real-world datasets. OBJECTIVES: The aim of this study was to assess the prevalence of complete revascularization and its association with longitudinal clinical outcomes in the U.S. Department of Veterans Affairs (VA) health care system using an automatically computed anatomic complexity score. METHODS: Patients undergoing percutaneous coronary intervention (PCI) between October 1, 2007, and September 30, 2020, were identified, and the burden of prerevascularization and postrevascularization ischemic disease was quantified using the VA SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score. The association between residual VA SYNTAX score and long-term major adverse cardiovascular events (MACE; death, myocardial infarction, repeat revascularization, and stroke) was assessed. RESULTS: A total of 57,476 veterans underwent PCI during the study period. After adjustment, the highest tertile of residual VA SYNTAX score was associated with increased hazard of MACE (HR: 2.06; 95% CI: 1.98-2.15) and death (HR: 1.50; 95% CI: 1.41-1.59) at 3 years compared to complete revascularization (residual VA SYNTAX score = 0). Hazard of 1- and 3-year MACE increased as a function of residual disease, regardless of baseline disease severity or initial presentation with acute or chronic coronary syndrome. CONCLUSIONS: Residual ischemic disease was strongly associated with long-term clinical outcomes in a contemporary national cohort of PCI patients. Automatically computed anatomic complexity scores can be used to assess the longitudinal risk for residual ischemic disease after PCI and may be implemented to improve interventional quality.

Trends and outcomes of percutaneous coronary intervention during the COVID-19 pandemic in Michigan.

BACKGROUND: The COVID-19 pandemic has severely impacted healthcare delivery and patient outcomes globally. AIMS: We aimed to evaluate the influence of the COVID-19 pandemic on the temporal trends and outcomes of patients undergoing percutaneous coronary intervention (PCI) in Michigan. METHODS: We compared all patients undergoing PCI in the BMC2 Registry between March and December 2020 ("pandemic cohort") with those undergoing PCI between March and December 2019 ("pre-pandemic cohort"). A risk-adjusted analysis of in-hospital outcomes was performed between the pre-pandemic and pandemic cohort. A subgroup analysis was performed comparing COVID-19 positive vs. negative patients during the pandemic. RESULTS: There was a 15.2% reduction in overall PCI volume from the pre-pandemic (n = 25,737) to the pandemic cohort (n = 21,822), which was more pronounced for stable angina and non-ST-elevation acute coronary syndromes (ACS) presentations, and between February and May 2020. Patients in the two cohorts had similar clinical and procedural characteristics. Monthly mortality rates for primary PCI were generally higher in the pandemic period. There were no significant system delays in care between the cohorts. Risk-adjusted mortality was higher in the pandemic cohort (aOR 1.26, 95% CI 1.07-1.47, p = 0.005), a finding that was only partially explained by worse outcomes in COVID-19 patients and was more pronounced in subjects with ACS. During the pandemic, COVID-19 positive patients suffered higher risk-adjusted mortality (aOR 5.69, 95% CI 2.54-12.74, p<0.001) compared with COVID negative patients. CONCLUSIONS: During the COVID-19 pandemic, we observed a reduction in PCI volumes and higher risk-adjusted mortality. COVID-19 positive patients experienced significantly worse outcomes.

Orbital atherectomy of calcified coronary ostial lesions.

OBJECTIVES: To evaluate the feasibility and safety of coronary orbital atherectomy (OA) for the treatment of calcified ostial lesions. BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly being completed in complex patients and lesions. OA is effective for severely calcified coronary lesions; however, there is a dearth of evidence on the use of OA in ostial lesions, especially with long-term outcome data. METHODS: Data were obtained from a retrospective analysis of patients who underwent OA of heavily calcified ostial lesions followed by stent implantation from December 2010 to June 2019 at two high-volume PCI centers. Kaplan-Meier analysis was utilized to assess the primary endpoints of 30-day, 1-year, and 2-year freedom-from (FF) major adverse cardiac events (MACE: death, myocardial infarction, or target vessel revascularization), stroke, and stent thrombosis (ST). RESULTS: A total of 56 patients underwent OA to treat heavily calcified ostial coronary lesions. The mean age was 72 years with a high prevalence of diabetes (55%) and heart failure (36%), requiring hemodynamic support (14%). There was high FF angiographic complications (93%), and at 30-day, 1-year, and 2-year, a high FF-MACE (96%, 91%, and 88%), stroke (98%, 96%, and 96%), and ST (100%), respectively. CONCLUSIONS: This study represents the largest real-world experience of coronary OA use in heavily calcified ostial lesions with long-term outcomes over 2 years. The main finding in this retrospective analysis is that, despite the complex patients and lesions included in this analysis, OA appears to be a feasible and safe treatment option for calcified coronary ostial lesions.

Cell Cycle Progression Score, but Not Phosphatase and Tensin Homolog Loss, Is an Independent Prognostic Factor for Metastasis in Intermediate- and High-risk Prostate Cancer in Men Treated With and Without Salvage Radiotherapy.

PURPOSE: The prognostic value for metastasis of the cell-cycle progression score and phosphatase and tensin homolog haven't been evaluated jointly in contemporary men with exclusively intermediate- or high-risk prostate cancer. We evaluated associations of cell-cycle progression and phosphatase and tensin homolog with metastasis-free survival in contemporary intermediate/high-risk prostate cancer patients overall, and intermediate/high-risk men receiving salvage radiotherapy. MATERIALS AND METHODS: In a case-cohort of 209 prostatectomy patients with intermediate/high-risk prostate cancer, and a cohort of 172 such men who received salvage radiotherapy, cell-cycle progression score was calculated from RNA expression, and phosphatase and tensin homolog was analyzed by immunohistochemistry. Proportional hazards regression, weighted for case-cohort design or unweighted for the salvage radiotherapy cohort, was used to evaluate associations of cell-cycle progression, phosphatase and tensin homolog with metastasis-free survival. Improvement in model discrimination was evaluated with the concordance index. RESULTS: In the case-cohort 41 men had metastasis, and 17 developed metastasis in the salvage radiotherapy cohort, at median follow-up of 3 and 4 years, respectively. For both case-cohort and salvage radiotherapy cohort, cell-cycle progression was independently associated with metastasis-free survival after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical: hazard ratio (95% confidence interval) = 3.11 (1.70-5.69) and 1.85 (1.19-2.85), respectively. Adding cell-cycle progression to Cancer of the Prostate Risk Assessment Post-Surgical increased the concordance index from 0.861 to 0.899 (case-cohort), and 0.745 to 0.819 (salvage radiotherapy cohort). Although statistically significant in univariate analyses, phosphatase and tensin homolog was no longer significant after adjustment for Cancer of the Prostate Risk Assessment Post-Surgical. Analysis of interaction with National Comprehensive Cancer Network risk group showed that cell-cycle progression had the strongest effect among unfavorable intermediate-risk men. CONCLUSIONS: In the first study to evaluate metastasis risk associated with cell-cycle progression and phosphatase and tensin homolog in exclusively intermediate/high-risk prostate cancer, and in such men with salvage radiotherapy, cell-cycle progression but not phosphatase and tensin homolog was associated with significantly increased 2- to 3-fold risk of metastasis after Cancer of the Prostate Risk Assessment Post-Surgical adjustment.

Radial versus femoral access for left main percutaneous coronary intervention: An analysis from the Veterans Affairs Clinical, Reporting, and Tracking Program.

OBJECTIVES: We aimed to compare clinical characteristics and procedural outcomes of left main percutaneous interventions (LM-PCI) by transradial (TRA) versus transfemoral (TFA) approach in the VA healthcare system. BACKGROUND: TRA for percutaneous coronary intervention (PCI) is steadily increasing. However, the frequency and efficacy of TRA for LM-PCI remain less studied. METHODS: All LM-PCIs performed in the VA healthcare system were identified for fiscal year 2008 through 2018. Patients' baseline characteristics and procedure-related variables were compared by access site. Both short- and long-term clinical outcomes were analyzed using propensity score matching. RESULTS: A total of 4004 LM-PCI were performed in the VA via either radial or femoral access from 2008 to 2018. Among these, 596 (14.9%) LM PCIs were performed via TRA. Use of TRA for LM-PCI increased from 2.2% to 31.5% over the study period. Propensity matched outcome analysis, comparing TRA versus TFA, showed a similar procedural success (98.4% for TRA vs. 97.8% for TFA; RR: 1.01 [0.98, 1.03]) and 1-year major adverse cardiovascular events (MACE) (25.9% for TRA vs. 26.8% TFA; RR: 0.96 [0.74, 1.25]). There were no statistically significant differences among secondary outcomes analyses including major bleeding. CONCLUSION: Use of TRA for LM-PCI has been steadily increasing in the VA healthcare system. These findings demonstrate similar procedural success and 1-year MACE across access strategies, suggesting an opportunity to continue increasing TRA use for LM-PCI.

Impact of Operator Volumes and Experience on Outcomes After Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment, Reporting and Tracking (CART) Program.

BACKGROUND: Recent analyses of the volume-outcome relationship for percutaneous coronary intervention (PCI) have suggested a less robust association than previously reported. It is unknown if novel factors such as lifetime operator experience influence this relationship. OBJECTIVES: To assess the relationship between annual volumes and outcomes for PCI and determine whether lifetime operator experience modulates the association. METHODS: Annual PCI volumes for facilities and operators within the Veterans Affairs Healthcare System and their relationship with 30-day mortality following PCI were described. The influence of operator lifetime experience on the volume-outcome relationship was assessed. Hierarchical logistic regression was used to adjust for patient and procedural factors. RESULTS: 57,608 PCIs performed from 2013 to 2018 by 382 operators and 63 institutions were analyzed. Operator annualized PCI volume averaged 47.6 (standard deviation [SD] 49.1) and site annualized volume averaged 189.2 (SD 105.2). Median operator experience was 9.0 years (interquartile range [IQR] 4.0-15.0). There was no independent relationship between operator annual volume, institutional volume, or operator lifetime experience with 30-day mortality (p > 0.10). However, the interaction between operator volume and lifetime experience was associated with a marginal decrease in mortality (odds ratio [OR] 0.9998, 95% CI 0.9996-0.9999). CONCLUSIONS: There were no significant associations between facility or operator-level procedural volume and 30-day mortality following PCI in a nationally integrated healthcare system. There was a marginal association between the interaction of operator lifetime experience, operator annual volume, and 30-day mortality that is unlikely to be clinically relevant, though does suggest an opportunity to explore novel factors that may influence the volume-outcome relationship.

Decision Support Needs for Patients with Severe Symptomatic Aortic Stenosis.

Social workers in healthcare settings often support patient decision-making processes for complex medical decisions. The objective of this study was to examine decision support needs for patients considering aortic valve replacement (AVR) for aortic stenosis. Seventeen qualitative interviews were conducted to explore treatment decision experiences of patients who accepted AVR. Analysis was conducted using a mixed inductive-deductive approach. Fear was a prevalent response for most participants in the face of AVR. Two general paths of decision making emerged: an "active" information seeking approach, or a "passive" simplicity seeking approach. Patients with unique clinical presentations felt alienated by the decision-making process. Acknowledging fear while understanding different decision-making styles provide opportunities for social workers and other members of multidisciplinary teams to support complex patient decisions.

Influence of Major Adverse Events on Procedural Selection for Percutaneous Coronary Intervention: Insights From the Veterans Affairs Clinical Assessment Reporting and Tracking Program.

Background: Public reporting of percutaneous coronary intervention (PCI) outcomes has been associated with risk-averse attitudes, and pressure to avoid negative outcomes may hinder the care of high-risk patients referred for PCI in public reporting environments. It is unknown whether the occurrence of PCI-related major adverse events (MAEs) influences future case selection in nonpublic reporting environments. Here, we describe trends in PCI case selection among patients undergoing coronary angiography following MAEs in Veterans Affairs (VA) cardiac catheterization laboratories participating in a mandatory internal quality improvement program without public reporting of outcomes. Methods: Patients who underwent coronary angiography between October 1, 2010, and September 30, 2018, were identified and stratified by VA 30-day PCI mortality risk. The association between MAEs and changes in the proportion of patients proceeding from coronary angiography to PCI within 14 days was assessed. Results: A total of 251,526 patients and 913 MAEs were included in the analysis. For each prespecified time period of 1, 2, and 4 weeks following an MAE, there were no significant changes in the proportion of patients undergoing coronary angiography who proceeded to PCI within 14 days for the overall cohort and for each tercile of VA 30-day PCI mortality risk. Conclusions: There were no deviations from routine PCI referral practices following MAEs in this analysis of VA cardiac catheterization laboratories. Nonpublic reporting environments and quality improvement programs may be influential in mitigating PCI risk-aversion behaviors.

Access Site Selection and Outcomes for Chronic Total Occlusion Percutaneous Coronary Interventions: Insights from the VA CART Program.

Background: There has been increasing use of transradial access (TRA) for non-chronic total occlusion (CTO) percutaneous coronary intervention (PCI). There are limited data on TRA for CTO PCI. The objectives of this study were to assess the temporal trends in the use of TRA versus transfemoral access (TFA), identify procedural and lesion characteristics associated with the use of TRA and TFA, and evaluate the association of access site with procedural complications and technical success among veterans undergoing attempted CTO PCI. Methods: We performed a retrospective analysis of veteran patients who underwent attempted CTO PCI to compare outcomes between TRA and TFA. Patients who had undergone attempted PCI of at least 1 CTO were included. Propensity score matching was used to evaluate the composite primary outcome of major procedural complications, in-hospital bleeding, or 30-day mortality and the secondary outcome of procedural success. Results: In total, 4609 patients underwent attempted CTO PCI during 2010-2017. Rates of TRA for CTO PCI increased significantly, from 7% in 2010 to 38% in 2017 (P trend < .01). A greater percentage of CTO lesions in the TFA group was calcified and >20.0 mm in length. TRA was not associated with a reduction in the composite primary outcome (TRA 3.3% vs TFA 4.0%, P = .47) or procedural success (TRA 66.6% vs TFA 65.7%, P = .74) compared with TFA. Conclusions: In this retrospective analysis of patients who underwent attempted CTO PCI, the proportion of TRA for CTO PCI has increased over time but was not associated with a greater safety or procedural success than TFA.

Clinical Characteristics and Outcomes Among Patients Undergoing High-Risk Percutaneous Coronary Interventions by Single or Multiple Operators: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

Background High-risk percutaneous coronary intervention (HR-PCI) is increasingly common among contemporary patients with coronary artery disease. Experts have advocated for a collaborative 2-operator approach to support intraprocedural decision-making for these complex interventions. The impact of a second operator on patient and procedural outcomes is unknown. Methods and Results Patients who underwent HR-PCI from 2015 to 2018 within the Veterans Affairs Healthcare System were identified. Propensity-matched cohorts were generated to compare the outcomes following HR-PCI performed by a single or multiple (≥2) operators. The primary end point was the 12-month rate of major adverse cardiovascular events. We identified 6672 patients who underwent HR-PCI during the study period; 6211 (93%) were treated by a single operator, and 461 (7%) were treated by multiple operators, with a nonsignificant trend toward increased multioperator procedures over time. A higher proportion of patients treated by multiple operators underwent left main (10% versus 7%, P=0.045) or chronic total occlusion intervention (11% versus 5%, P<0.001). Lead interventionalists participating in multioperator procedures practiced at centers with higher annual HR-PCI volumes (124±71.3 versus 111±69.2; standardized mean difference, 0.197; P<0.001) but otherwise performed a similar number of HR-PCI procedures per year (34.4±35.3 versus 34.7±30.7; standardized mean difference, 0.388; P=0.841) compared with their peers performing single-operator interventions. In a propensity-matched cohort, there was no significant difference in major adverse cardiovascular events (32% versus 30%, P=0.444) between patients who underwent single-operator versus multioperator HR-PCI. Adjusted analyses accounting for site-level variance showed no significant differences in outcomes. Conclusions Patients who underwent multioperator HR-PCI had similar outcomes compared with single-operator procedures. Further studies are needed to determine if the addition of a second operator offers clinical benefits to a subset of HR-PCI patients undergoing left main or chronic total occlusion intervention.

Dissemination of Transcatheter Aortic Valve Replacement in the United States.

BACKGROUND: Societal guidelines and payor coverage decisions for transcatheter aortic valve replacement (TAVR) attempt to strike a balance between providing access and maintaining quality. The extent to which dissemination of TAVR has achieved these ideals remains unknown. OBJECTIVES: This study sought to define patterns of TAVR dissemination in the United States and their influence on outcomes. METHODS: Using data from the TVT (Transcatheter Valvular Therapy) registry, this study identified TAVR sites from 2011 to 2018 and calculated drive-times from existing to new sites. In a contemporary cohort, this study compared site and patient characteristics by annual case volume and density of sites per million Medicare beneficiaries. Using hierarchical regression and Cox methods, this study determined the association between case volumes, site density, and changes in volume and density with patient risk profiles and outcomes. RESULTS: TAVR sites participating in the TVT registry increased from 198 to 556 from 2011 to 2018. Median drive-time from existing to new sites decreased from 403 minutes (interquartile range: 211-587 minutes) to 26 minutes (interquartile range: 17-48 minutes). In a contemporary cohort, higher site density was associated with lower procedural risk as well as with an increased hazard of 30-day risk-adjusted mortality (P = 0.017). Similarly, longitudinal increases in site density over time were associated with a higher hazard of 30-day (P = 0.011) and 1-year (P = 0.013) mortality. CONCLUSIONS: TAVR has expanded significantly over time, but with regional clustering of sites. Although procedural risk is lower at higher density sites, these sites demonstrate an increased hazard of mortality. These findings suggest that the expansion of TAVR services in the United States may have had unintended consequences on procedural quality.

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

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.