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Differential classification of prostate cancer (CaP) grade group (GG) 2 and 3 tumors remains challenging, likely due to the subjective quantification of percentage of Gleason pattern 4 (%GP4). Artificial intelligence assessment of %GP4 may improve its accuracy and reproducibility and provide information for prognosis prediction. To investigate this potential, a convolutional neural network (CNN) model was trained to objectively identify and quantify Gleason pattern (GP) 3 and 4 areas, estimate %GP4, and assess whether CNN-assessed %GP4 is associated with biochemical recurrence (BCR) risk in intermediate risk GG 2 and 3 tumors. The study was conducted in a radical prostatectomy cohort (1999–2012) of African American men from the Henry Ford Health System (Detroit, Michigan). A CNN model that could discriminate four tissue types (stroma, benign glands, GP3 glands, and GP4 glands) was developed using histopathologic images containing GG 1 (n = 45) and 4 (n = 20) tumor foci. The CNN model was applied to GG 2 (n = 153) and 3 (n = 62) for %GP4 estimation, and Cox proportional hazard modeling was used to assess the association of %GP4 and BCR, accounting for other clinicopathologic features including GG. The CNN model achieved an overall accuracy of 86% in distinguishing the four tissue types. Further, CNN-assessed %GP4 was significantly higher in GG 3 compared with GG 2 tumors (p = 7.2*10− 11). %GP4 was associated with an increased risk of BCR (adjusted HR = 1.09 per 10% increase in %GP4, p = 0.010) in GG 2 and 3 tumors. Within GG 2 tumors specifically, %GP4 was more strongly associated with BCR (adjusted HR = 1.12, p = 0.006). Our findings demonstrate the feasibility of CNN-assessed %GP4 estimation, which is associated with BCR risk. This objective approach could be added to the standard pathological assessment for patients with GG 2 and 3 tumors and act as a surrogate for specialist genitourinary pathologist evaluation when such consultation is not available.

Green turtle ( Chelonia mydas ) embryos are in an arrested state of development when the eggs are laid, but in the presence of oxygen, arrest is broken and development resumes within 12–16 h. However, the precise oxygen level at which embryos break arrest and continue development is not known. To better understand the impact of oxygen concentration on breaking of arrest and early embryonic development, we incubated freshly laid eggs of the green sea turtle for three days at each of six different oxygen concentrations (less than or equal to 1%, 3%, 5%, 7%, 9% and 21%) and monitored the appearance and growth of white spots on the shell, indicative of embryonic development. As reported previously, white spots did not develop on eggs incubated in anoxia (less than or equal to 1% oxygen). For all other treatments, mean time to white spot detection and white spot growth rate varied inversely with oxygen concentration. In nearly all cases the difference between eggs at different oxygen levels was statistically significant ( p ≤ 0.05). This suggests that sea turtle embryonic development may respond to oxygen in a dose-dependent manner. Our results indicate that the development of green turtle embryos may be slowed if they are exposed to the most hypoxic conditions reported in mature natural nests.

Introduction: Prostate cancer is a heterogenous multifocal disease. We hypothesize that different tumor foci may harbor distinct driver molecular aberrations, making it a more complex disease and difficult to manage. To avoid overlooking smaller tumor foci with clinical and biological significance, we used an innovative approach to understand the genetic underpinnings of each tumor foci based on the molecular analysis of whole-mount radical prostatectomy specimens rather than a systematic sampling of dominant nodules alone. Our study aimed to identify distinct molecular subsets of prostate cancer, if any, and correlate them with clinical outcomes in Caucasians (CA) and African Americans (AA). Method: We randomly selected 834 whole-mount radical prostatectomy tissues including 463 (56%) CA and 371 (44%) AA. We used combined dual immunohistochemistry (IHC) for ERG and SPINK1 and dual RNA in-situ hybridization (ISH) for ETV1 and ETV4. The racial disparity in aberrant oncogene expression was analyzed by the Chi-squared test. The recurrence-free survival (RFS) of patients with distinct molecular subsets of prostate cancer was examined by the Kaplan-Meier method and cox-ph models. The Gleason’s grades of prostate biopsies were summarized by spaghetti plot and compared by linear mixed models. Results: Patients with localized prostate cancer expressing none, one, two, and three of four oncogenes were 16.4%, 58.4%, 21.7%, and 3.5%, respectively. The expression of ERG and SPINK1 was negatively correlated (odds ratio (OR)=0.38, 95% CI 0.29-0.51, p Conclusion: Our findings showed the molecular heterogeneity between CA and AA who had localized prostate cancer, and supported ETV1 and ETV4 as prognostic markers that can be incorporated into clinical practice to better predict prostate cancer recurrence after radical prostatectomy in CA and AA, respectively. Citation Format: Wei Zhao, Pin Li, Shannon Carskadon, Craig Rogers, James Peabody, Mani Menon, Dhananjay Chitale, Sean Williamson, Nilesh Gupta, Nallasivam Palanisamy. New perspective on racial disparities in prostate cancer: identification of new molecular subsets using whole-mount radical prostatectomy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5762.

Introduction: African Americans (AA) had a higher mortality from prostate cancer than Caucasian Americans (CA). The racial disparity in the outcome of prostate cancer is explained by socioeconomic factors. However, if equally accessible to standard care, whether AA with prostate cancer have an inferior outcome than CAs remains unknown. To understand the biochemical recurrence free survival (RFS) after radical prostatectomy in a racial disparity perspective, we analyzed a large cohort of patients and made important observations. Method: AA (n=1020) and CA (n=1263) who received prostatectomy for prostate cancer were included. Their demographic and clinicopathologic characteristics were compared using the Chi-squared test and the Wilcox-rank test. RFS between AA and CA was compared using Kaplan-Meier curves with stratified log-rank test and cox-ph models. The Gleason grade across multiple biopsies was summarized by spaghetti plot and compared by linear mixed models. Results: Compared with CA, AA were younger at the time of prostatectomy (60.5 vs 62 years), had higher pre-operative PSA levels (5.7 vs 5.3 ng/mL), were fewer with Gleason grade of 5 (7.9% vs 13.3%) and lymph node metastasis (6.1% vs 9.5%), and waited longer from biopsy to prostatectomy (3 vs 2.3 months)(all p Conclusion: Our data showed that contrary to common belief, AA had a better RFS than CA after receiving prostatectomy. This study further supported the underlying biological difference of prostate cancer between AA and CA that requires future studies to elucidate. RFS Summary HR Race African American 1020 (44.7) - Caucasian 1263 (55.3) 1.25 (1.00-1.58, p=0.05) Pre-operative PSA (ng/mL) Mean (SD) 7.5 (9.0) 1.01 (1.01-1.02, p Citation Format: Pin Li, Wei Zhao, Shannon Carskadon, Craig Rogers, James Peabody, Mani Menon, Dhananjay Chitale, Sean Williamson, Nilesh Gupta, Nallasivam Palanisamy. Racial differences in clinical outcome in patients treated for clinically localized prostate cancer by radical prostatectomy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 747.

Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.

Cancer datasets recommend standardised reporting of histopathological data items with elements categorised as either core (required) or non-core (recommended), irrespective of the clinical scenario. However, the clinical significance of a data item in an individual case would depend on the clinicopathological setting as well as local management guidelines. A data item that is critical for patient management in one clinical scenario may be largely irrelevant in another patient. Pathologists must understand how their data are used in clinical practice so that they can focus their limited resources appropriately. We briefly review the use of histopathological data in the management of urological cancers, highlighting scenarios where a data item may be of limited clinical utility.

Aims. Histopathologic benign mimickers of prostate cancer have mostly focused on glandular mimics, with non-glandular mimics mainly limited to inflammatory conditions. While there is a paucity of literature recognizing small cystic (presumably artifactual) spaces in transurethral resection specimens, in some instances they can become florid enough to mimic vascular or epithelial neoplasms. Herein, we detailed histologic, immunophenotypic, and clinicopathologic findings in a large series of specimens showing prominent diagnostically confounding cystic spaces. Methods and Results. Sixty specimens were obtained (50 transurethral resections, 7 aquablations, 3 laser enucleations), from 17 different surgeons. Seven specimens had concurrent genitourinary pathology (4 prostatic adenocarcinoma, 1 solitary fibrous tumor, 1 prostatic atypia, 1 urothelial carcinoma in situ). The extent of cystic change among overall tissue examined ranged from 1 mm-8 mm (mean 3.4 mm), with luminal content of cystic spaces characterized as empty (72%), both empty and fluid-like (17%), and both empty and mucin-like (11%; mucin histochemical stain was negative on all specimens). Notable differences in degree of tissue cautery artifact or inflammation was not found. Immunohistochemistry performed on 30 specimens showed cystic spaces negative for S100, ERG, pankeratin, and CD45. Conclusion. Although artifactual in nature, in some instances small cystic spaces encountered in prostatic transurethral resections and more novel related procedures can become florid enough to warrant recognition as a potential diagnostic confounder of vascular or epithelial neoplasms.

268 Background: Invasive cribriform and intraductal carcinoma (CF/IDC) portends an unfavorable prognosis for patients diagnosed with prostate cancer (CaP). Limited studies with small sample sizes have explored whether genomic classifiers are associated with IDC and/or CF status. We investigated the correlation between Decipher genomic risk score and IDC/CF status and assessed PCa transcriptomic features. Methods: We performed a retrospective review of CaP patients who had Decipher testing at a single high volume center between 2009-2020. The highest grade index lesion from radical prostatectomy specimens was identified by GU pathologists and used for Decipher testing. Genitourinary pathologists reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were divided into three groups based on pathologic features, absent CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Multivariable logistic regression was used to identify predictors of high-risk Decipher GC scores. The Kaplan-Meier method with log-rank was used to compare biochemical recurrence free survival. Differential gene expression and gene network analysis was used to identify genes and pathways associated with IDC/CF features. Results: 463 patients were included with a median follow-up of 25 months. Patients who were CF+/IDC+ had higher GC scores (CF+/IDC+: 0.77 vs. CF+/IDC-: 0.71 vs. CF-/IDC-: 0.61, p3 (CF+/IDC+: 79% vs. CF+/IDC-: 52% vs. CF-/IDC-: 52%, p3 (OR: 1.58, p=0.04). Transcriptomic analysis revealed that the hallmark androgen response pathway was significantly upregulated in CF+/IDC+ patients (Log fold change: 15.7, p

An alternative wing sail section shape was developed as a potential improvement to either a soft sail or the common NACA00XX section used on some small autonomous sailing craft. The prototype wing was developed as an evolution of a traditional square sail. Evaluation included wind tunnel and on-the-water tests followed by performance estimates from a Velocity Prediction Program. The test vessel was the 1.2 m long Version 2 MaxiMOOP. Advantages of the wing sail over the current voyaging soft sail design include: higher speeds in some conditions, increased durability, increased buoyancy in the case of capsizing, and easier implementation of control systems. Some potential theoretical advantage was found over the NACA0009.

GDF15 (growth/differentiation factor 15), also known as MIC-1 (Macrophage inhibitory cytokine 1), is a divergent member of the TGFβ superfamily of cytokines and is highly expressed in prostate tumors, but its role in prostate carcinogenesis and utility as a prognostic biomarker is unclear. We studied 91 prostate cancer cases that underwent surgery as their primary treatment and were then subsequently followed for biochemical recurrence (BCR). These cases also had a benign prostate biopsy at least one year before their prostate cancer diagnosis. In both the benign biopsy and tumor specimens, we quantified the intensity of GDF15 expression and characterized the presence of tumor associated macrophages by measuring the density of CD68-positive stained cells, and the M2 macrophage marker CD204 by immunohistochemical analysis. Marker expression was measured in prostate a) benign biopsy (BS), b) tumor-adjacent benign (BGS) and c) tumor tissue (MGS) using an automated multi-image processing macro developed in the ImageJ software. A Cox proportional hazards model was used to test the association of time to BCR of the low expression group compared with medium or high biomarker expression. The risk of BCR differed with the extent of GDF15 expression in the prostatic epithelial tissue of benign and tumor regions of the prostate. For instance, in BGS, high expression of GDF15 was associated with increased risk of BCR (hazard ratio (HR)=2.58, p=0.07). After controlling for PSA at diagnosis, Gleason grade and pathologic stage, high expression of GDF15 in BGS had a stronger association with BCR (HR=3.30, p=0.04). The risk of BCR increased with increasing level of infiltration of CD204/CD68 positive macrophages in BGS (HR=4.19, p=0.02) and MGS (HR=4.16, p=0.01) even after controlling for PSA at diagnosis, Gleason grade and pathologic stage. The combined expression levels of GDF15 and CD204/CD68 showed that prostate cancer cases with small GDF15 expression changes between BGS and MGS and high CD204/CD68 expression in BGS were at 3-fold higher risk of BCR (HR=3.67, p=0.05). In summary, expression levels of GDF15 and CD204 M2 macrophages in different regions of the prostate can change as the disease progresses from benign to a tumorigenic state and serve as markers for aggressive disease. Further evaluation of these dynamic differences in the prostate immune cellular profile in the pre-malignant and malignant state may offer additional insight into inflammatory-mediated prostate carcinogenesis. Citation Format: Sudha M. Sadasivan, Yalei Chen, Nilesh Gupta, Sean Williamson, Dhananjay Chitale, Xiaoxia Han, Kevin Bobbitt, Andrew Rundle, Deliang Tang, Benjamin A. Rybicki. Changes in GDF15 (growth/differentiation factor 15) expression and M2 macrophages during prostate carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2337.

Never events are defined as ‘serious, largely preventable, patient safety incidents that should not occur if the available preventative measures have been implemented by healthcare providers’.1–3 T...