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Background: African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. Patients and methods: We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. Results: No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Conclusion: Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

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This study aimed to develop a noninvasive Machine Learning (ML) model to identify clinically significant prostate cancer (csPCa) according to Gleason Score (GS) based on biparametric MRI (bpMRI) radiomic features and clinical information. METHODS: This retrospective study included 86 adult Hispanic men (60 ± 8.2 years, median prostate-specific antigen density (PSA-D) 0.15 ng/mL2) with PCa who underwent prebiopsy 3T MRI followed by targeted MRI-ultrasound fusion and systematic biopsy. Two observers performed 2D segmentation of lesions in T2WI/ADC images. We classified csPCa (GS ≥ 7) vs. non-csPCa (GS = 6). Univariate statistical tests were performed for different parameters, including prostate volume (PV), PSA-D, PI-RADS, and radiomic features. Multivariate models were built using the automatic feature selection algorithm Recursive Feature Elimination (RFE) and different classifiers. A stratified split separated the train/test (80%) and validation (20%) sets. RESULTS: Radiomic features derived from T2WI/ADC are associated with GS in patients with PCa. The best model found was multivariate, including image (T2WI/ADC) and clinical (PV and PSA-D) information. The validation area under the curve (AUC) was 0.80 for differentiating csPCa from non-csPCa, exhibiting better performance than PI-RADS (AUC: 0.71) and PSA-D (AUC: 0.78). CONCLUSION: Our multivariate ML model outperforms PI-RADS v2.1 and established clinical indicators like PSA-D in classifying csPCa accurately. This underscores MRI-derived radiomics' (T2WI/ADC) potential as a robust biomarker for assessing PCa aggressiveness in Hispanic patients.

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BACKGROUND: Prostate carcinoma is the second leading cause of cancer and the fifth cause of cancer death in men worldwide. OBJECTIVE: To know high-grade prostatic intraepithelial neoplasia and prostate acinar adenocarcinoma immunohistochemical profiles. MATERIAL AND METHODS: Observational, analytical, cross-sectional, retrospective study of specimens obtained by cutting needle biopsy and prostate resection from subjects diagnosed with acinar adenocarcinoma of the prostate and high-grade prostatic intraepithelial neoplasia between January 2015 and December 2020. Tissue microarrays were performed and, subsequently, immunohistochemical studies for BCL2, EGFR, p53, Her2/neu and Ki67. Descriptive statistics were used to analyze clinicopathological factors. Qualitative variables were compared with Fisher's exact test. RESULTS: Twenty-three patients were studied; eight (34%) with angiolymphatic invasion, 14 (60.8%) with perineural invasion, five (21.2%) with prostatitis, and four (17.3%) with fibroadenomatous hyperplasia. HER2/neu (p = 0.1023), p53 (p = 1) and BCL2 expression (p = 0.4136) was observed. CONCLUSION: HER2/neu increased expression was identified in high-grade prostatic intraepithelial neoplasia and acinar adenocarcinoma of the prostate.

ANTECEDENTES: En el mundo, el carcinoma de próstata constituye la segunda causa de cáncer y la quinta causa de muerte por cáncer en hombres. OBJETIVO: Conocer el perfil inmunohistoquímico de la neoplasia intraepitelial prostática de alto grado y del adenocarcinoma acinar de próstata. MATERIAL Y MÉTODOS: Estudio observacional, analítico, transversal y retrospectivo de especímenes obtenidos por biopsia con aguja cortante y resección de próstata debido a diagnóstico de adenocarcinoma acinar de próstata y neoplasia intraepitelial de alto grado, entre enero de 2015 y diciembre de 2020. Se realizaron microarreglos tisulares y, posteriormente, estudios de inmunohistoquímica para BCL2, EGFR, p53, Her2/neu y Ki67. Se realizó estadística descriptiva para analizar los factores clinicopatológicos; las variables cualitativas se compararon con prueba exacta de Fisher. RESULTADOS: Se estudiaron 23 pacientes, ocho (34 %) con invasión angiolinfática, 14 (60.8 %) con invasión perineural, cinco (21.2 %) con prostatitis y cuatro (17.3 %) con hiperplasia fibroadenomatosa. Se observó expresión de HER2/neu (p = 0.1023), p53 (p = 1) y BCL2 (p = 0.4136). CONCLUSIÓN: Se identificó mayor expresión de HER2/neu en la neoplasia intraepitelial prostática de alto grado y el adenocarcinoma acinar de próstata.

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Resumen Antecedentes: En el mundo, el carcinoma de próstata constituye la segunda causa de cáncer y la quinta causa de muerte por cáncer en hombres. Objetivo: Conocer el perfil inmunohistoquímico de la neoplasia intraepitelial prostática de alto grado y del adenocarcinoma acinar de próstata. Material y métodos: Estudio observacional, analítico, transversal y retrospectivo de especímenes obtenidos por biopsia con aguja cortante y resección de próstata debido a diagnóstico de adenocarcinoma acinar de próstata y neoplasia intraepitelial de alto grado, entre enero de 2015 y diciembre de 2020. Se realizaron microarreglos tisulares y, posteriormente, estudios de inmunohistoquímica para BCL2, EGFR, p53, Her2/neu y Ki67. Se realizó estadística descriptiva para analizar los factores clinicopatológicos; las variables cualitativas se compararon con prueba exacta de Fisher. Resultados: Se estudiaron 23 pacientes, ocho (34 %) con invasión angiolinfática, 14 (60.8 %) con invasión perineural, cinco (21.2 %) con prostatitis y cuatro (17.3 %) con hiperplasia fibroadenomatosa. Se observó expresión de HER2/neu (p = 0.1023), p53 (p = 1) y BCL2 (p = 0.4136). Conclusión: Se identificó mayor expresión de HER2/neu en la neoplasia intraepitelial prostática de alto grado y el adenocarcinoma acinar de próstata.

Abstract Background: Prostate carcinoma is the second leading cause of cancer and the fifth cause of cancer death in men worldwide. Objective: To know high-grade prostatic intraepithelial neoplasia and prostate acinar adenocarcinoma immunohistochemical profiles. Material and methods: Observational, analytical, cross-sectional, retrospective study of specimens obtained by cutting needle biopsy and prostate resection from subjects diagnosed with acinar adenocarcinoma of the prostate and high-grade prostatic intraepithelial neoplasia between January 2015 and December 2020. Tissue microarrays were performed and, subsequently, immunohistochemical studies for BCL2, EGFR, p53, Her2/neu and Ki67. Descriptive statistics were used to analyze clinicopathological factors. Qualitative variables were compared with Fisher's exact test. Results: Twenty-three patients were studied; eight (34%) with angiolymphatic invasion, 14 (60.8%) with perineural invasion, five (21.2%) with prostatitis, and four (17.3%) with fibroadenomatous hyperplasia. HER2/neu (p = 0.1023), p53 (p = 1) and BCL2 expression (p = 0.4136) was observed. Conclusion: HER2/neu increased expression was identified in high-grade prostatic intraepithelial neoplasia and acinar adenocarcinoma of the prostate.

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Background: Prostate carcinoma is the second leading cause of cancer and the fifth cause of cancer death in men worldwide. Objective: To know high-grade prostatic intraepithelial neoplasia and prostate acinar adenocarcinoma immunohistochemical profiles. Material and methods: Observational, analytical, cross-sectional, retrospective study of specimens obtained by cutting needle biopsy and prostate resection from subjects diagnosed with acinar adenocarcinoma of the prostate and high-grade prostatic intraepithelial neoplasia between January 2015 and December 2020. Tissue microarrays were performed and, subsequently, immunohistochemical studies for BCL2, EGFR, p53, Her2/neu and Ki67. Descriptive statistics were used to analyze clinicopathological factors. Qualitative variables were compared with Fisher's exact test. Results: Twenty-three patients were studied; eight (34%) with angiolymphatic invasion, 14 (60.8%) with perineural invasion, five (21.2%) with prostatitis, and four (17.3%) with fibroadenomatous hyperplasia. HER2/neu (p = 0.1023), p53 (p = 1) and BCL2 expression (p = 0.4136) was observed. Conclusion: HER2/neu increased expression was identified in high-grade prostatic intraepithelial neoplasia and acinar adenocarcinoma of the prostate.

Antecedentes: En el mundo, el carcinoma de próstata constituye la segunda causa de cáncer y la quinta causa de muerte por cáncer en hombres. Objetivo: Conocer el perfil inmunohistoquímico de la neoplasia intraepitelial prostática de alto grado y del adenocarcinoma acinar de próstata. Material y métodos: Estudio observacional, analítico, transversal y retrospectivo de especímenes obtenidos por biopsia con aguja cortante y resección de próstata debido a diagnóstico de adenocarcinoma acinar de próstata y neoplasia intraepitelial de alto grado, entre enero de 2015 y diciembre de 2020. Se realizaron microarreglos tisulares y, posteriormente, estudios de inmunohistoquímica para BCL2, EGFR, p53, Her2/neu y Ki67. Se realizó estadística descriptiva para analizar los factores clinicopatológicos; las variables cualitativas se compararon con prueba exacta de Fisher. Resultados: Se estudiaron 23 pacientes, ocho (34 %) con invasión angiolinfática, 14 (60.8 %) con invasión perineural, cinco (21.2 %) con prostatitis y cuatro (17.3 %) con hiperplasia fibroadenomatosa. Se observó expresión de HER2/neu (p = 0.1023), p53 (p = 1) y BCL2 (p = 0.4136). Conclusión: Se identificó mayor expresión de HER2/neu en la neoplasia intraepitelial prostática de alto grado y el adenocarcinoma acinar de próstata.

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INTRODUCTION: Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) improves prostate cancer staging. Furthermore, the intensity of intraprostatic uptake of PSMA can predict clinically relevant oncologic outcomes. The objective of this study is to evaluate whether the intensity of PSMA uptake is associated with clinically significant prostate cancer and to determine which value of PSMA uptake best discriminates this relationship. METHODS: A cohort study of 40 patients with biopsy-proven prostate cancer prior to external radiotherapy was conducted. The correlation between intraprostatic PSMA uptake intensity and adverse pathological findings in prostate biopsy was evaluated. Which PSMA uptake value better discriminates clinically significant prostate cancer was assessed using ROC curves. RESULTS: Forty percent of the patients had a clinically significant prostate cancer and the maximum standardized uptake value (SUV max) had a mean of 11.5 (SD ± 7). The sample showed a Spearman correlation coefficient of 0.4 (p = 0.007). The area under the curve (AUC) was 0.73 and a SUV max = 9.5 showed a sensitivity of 0.81 and a specificity of 0.71 in the detection of clinically significant prostate cancer. CONCLUSION: Intraprostatic PSMA uptake intensity can be a new diagnostic tool in the detection of clinically significant prostate cancer. An uptake intensity equal or greater than 9.5 is correlated with clinically significant prostate cancer.

Introducción: La tomografía por emisión de positrones (PET) con antígeno de membrana específico de próstata (PSMA) mejora la estadificación del cáncer de próstata. Además, la intensidad de captación intraprostática del PSMA puede predecir resultados oncológicos clínicamente relevantes. Nuestro objetivo fue evaluar si la intensidad de captación de PSMA se asocia con el cáncer de próstata clínicamente significativo y poder conocer qué valor de captación de PSMA discrimina mejor esta relación. Métodos: Se realizó un estudio de cohorte de 40 pacientes con cáncer de próstata comprobado por biopsia previo a la realización de radioterapia externa. Se evaluó correlación entre intensidad de captación del PSMA intraprostático y los resultados patológicos adversos en la biopsia prostática. Se estudió qué valor de captación de PSMA discrimina mejor el cáncer de próstata clínicamente significativo utilizando curvas ROC. Resultados: El 40% de los pacientes tuvieron un cáncer de próstata clínicamente significativo, el maximum standardized uptake value (SUV max) tuvo una media de 11.5 (DE ± 7). La muestra arrojó un coeficiente de correlación Spearman de 0.4 (p = 0.007). El área bajo la curva (AUC) fue de 0.73, mostrando el punto de corte un SUV max = 9.5, sensibilidad 0.81 y especificidad 0.71 en la detección de cáncer de próstata clínicamente significativo. Conclusión: la intensidad de captación del PSMA intraprostático puede ser una nueva herramienta diagnóstica en la detección del cáncer de próstata clínicamente significativo. Una intensidad de captación = 9.5 tuvo una buena correlación con el cáncer de próstata clínicamente significativo.

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Resumen Introducción: La tomografía por emisión de positrones (PET) con antígeno de membrana específico de próstata (PSMA) mejora la estadificación del cáncer de próstata. Además, la intensidad de captación intraprostática del PSMA puede predecir resultados oncológicos clínicamente relevantes. Nuestro objetivo fue evaluar si la intensidad de captación de PSMA se asocia con el cáncer de próstata clínicamente significativo y poder conocer qué valor de captación de PSMA discrimina mejor esta relación. Métodos: Se realizó un estudio de cohorte de 40 pacientes con cáncer de próstata comprobado por biopsia previo a la realización de radioterapia externa. Se evaluó correlación entre intensidad de captación del PSMA intraprostático y los resulta dos patológicos adversos en la biopsia prostática. Se estudió qué valor de captación de PSMA discrimina mejor el cáncer de próstata clínicamente significativo utilizando curvas ROC. Resultados: El 40% de los pacientes tuvieron un cáncer de próstata clínicamente significativo, el maximum standardized uptake value (SUV max) tuvo una media de 11.5 (DE ± 7). La muestra arrojó un coeficiente de correlación Spearman de 0.4 (p = 0.007). El área bajo la curva (AUC) fue de 0.73, mostrando el punto de corte un SUV max ≥ 9.5, sensibilidad 0.81 y especificidad 0.71 en la detección de cáncer de próstata clínicamente significativo. Conclusión: la intensidad de captación del PSMA intraprostático puede ser una nueva herramienta diagnóstica en la detección del cáncer de próstata clínicamente significativo. Una intensidad de captación ≥ 9.5 tuvo una buena correlación con el cáncer de próstata clínicamente significativo.

Abstract Introduction: Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) improves prostate cancer staging. Furthermore, the intensity of intraprostatic uptake of PSMA can predict clinically relevant oncologic outcomes. The objective of this study is to evaluate whether the intensity of PSMA uptake is associated with clinically significant prostate cancer and to determine which value of PSMA uptake best dis criminates this relationship. Methods: A cohort study of 40 patients with biopsy-proven prostate cancer prior to external radiotherapy was conducted. The correlation between intraprostatic PSMA uptake intensity and adverse pathological findings in prostate biopsy was evaluated. Which PSMA uptake value better discriminates clinically significant prostate cancer was assessed using ROC curves. Results: Forty percent of the patients had a clinically significant prostate cancer and the maximum standardized uptake value (SUV max) had a mean of 11.5 (SD ± 7). The sample showed a Spearman correlation coefficient of 0.4 (p = 0.007). The area under the curve (AUC) was 0.73 and a SUV max ≥ 9.5 showed a sensitivity of 0.81 and a specificity of 0.71 in the detection of clinically significant prostate cancer. Conclusion: Intraprostatic PSMA uptake intensity can be a new diagnostic tool in the detection of clinically significant prostate cancer. An uptake intensity equal or greater than 9.5 is correlated with clinically significant prostate cancer.

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The Gleason grade system is the main standard to quantify the aggressiveness and progression of prostate cancer. Currently, exists a high disagreement among experts in the diagnosis and stratification of this disease. Deep learning models have emerged as an alternative to classify and support experts automatically. However, these models are limited to learn a rigid stratification rule that can be biased during training to a specific observer. Therefore, this work introduces an embedding representation that integrates an auxiliary task learning to deal with the high inter and intra appearance of the Gleason system. The proposed strategy implements as a main task a triplet loss scheme that builds a feature embedding space with respect to batches of positive and negative histological training patches. As an auxiliary task is added a cross-entropy that helps with inter-class variability of samples while adding robust representations to the main task. The proposed approach shows promising results achieving an average accuracy of 66% and 64%, for two experts without statistical difference. Additionally, reach and average accuracy of 73% in patches where both pathologists are agree, showing the robustness patterns learning from the approach.

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BACKGROUND: Prostate cancer screening has reduced its mortality in 21%. However, this has also led to an increased number of biopsies in order to establish the diagnosis, many of them unnecessary. Current screening guidelines prioritize use of prostatic magnetic resonance and new biomarkers to reduce unnecessary biopsies, however, their implementation in developing countries screening programs is mainly limited by its costs. OBJECTIVE: We aimed to evaluate Prostate Biopsy Risk Collaborative Group (PBCG) and Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) 2.0 predictions accuracy in Mexican patients in order to guide prostate biopsy decision making and reduce unnecessary biopsies. MATERIALS AND METHODS: We retrospectively analyzed patients between 55 and 90 years old who underwent prostate biopsy in a high-volume center in Mexico between January 2017 and June 2020. Clinical utility of PBCG and PCPTRC 2.0 to predict high-grade prostate cancer (HGPCa) biopsy outcomes was evaluated using decision curve analysis and compared to actual biopsy decision making. Receiver operating characteristics area under the curve (AUC) was used to measure discrimination and external validation. RESULTS: From 687 patients eligible for prostate biopsy, 433 met selections criteria. One hundred and thirty-five (31.17%) patients were diagnosed with HGPCa, 63 (14.54%) with low-grade disease and 235 (54.27%) had a negative biopsy. PCPTRC 2.0 ≥15% threshold got a standardized net benefit (sNB) of 0.70, while PBCG ≥30% and ≥35% had a sNB of 0.27 and 0.15, respectively. Use of both models for guiding prostate biopsy decision resulted in no statistical difference for HGCPa detection rates, while achieved a significant difference in reducing total and unnecessary biopsies. However, this difference was lower (better) for PCPTRC 2.0, being statistically significative when compared against PBCG thresholds. Both models were well calibrated (AUC 0.79) and achieved external validation compared with international cohorts. CONCLUSIONS: Our study is the first to effectively validate both PCPTRC 2.0 and PBCG predictions for the Mexican population, proving that their use in daily practice improves biopsy decision making by accurately predicting HGPCa and limit unnecessary biopsies without representing additional costs to screening programs.

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During initial risk assessments, the metastatic potential of prostate cancer (PCa) may not be fully considered. The tumor's multicentric origin, which is associated with genetic mutations, may explain existing treatment limitations. Investigating human epidermal growth factor receptor 2 (HER2) expression in patients with different stages of PCa may therefore increase understanding of the mechanisms associated with the development of castration resistance. The present study examined the association between HER2 expression and the histologic features of PCa subjected to radical prostatectomy (RP) and evaluated the role of testosterone suppression in HER2 expression. In group 1, specimens from individuals who underwent RP without prior neoadjuvant androgen deprivation therapy (ADT) were included (n=42). In group 2 (PCa with ADT), specimens from individuals who underwent RP and received neoadjuvant cyproterone acetate during distinct periods (200 mg daily for 1-24 months) were included (n=150; cohort derived from a previous study). Immunohistochemical expression of HER2 was associated with prognostic factors such as perineural invasion, extra-prostatic disease, T stage, serum prostate-specific antigen (PSA), angiolymphatic invasion and surgical margins. Univariate regression analysis indicated that perineural invasion, PSA, International Society of Urological Pathology, angiolymphatic invasion, margin, T stage and neoadjuvant ADT was associated with HER2 expression. Ordinal regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (P<0.001). In addition, regression analysis indicated a significant effect of neoadjuvant ADT alone on HER2 expression (odd ratio=0.01; 95% CI, 0.00, 0.02; P<0.001). HER2 was expressed in PCa samples but was not associated with known prognostic factors. The use of short-acting ADT and the consequent blockage of testosterone effect may suppress the expression of HER2 in PCa cells.

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Prostate cancer (PCa) is characterized as being histologically and molecularly heterogeneous; however, this is not only incorrect among individuals, but also at the multiple foci level, which originates in the prostate gland itself. The reasons for such heterogeneity have not been fully elucidated; however, understanding these may be crucial in determining the course of the disease. PCa is characterized by a complex network of chromosomal rearrangements, which simultaneously deregulate multiple genes; this could explain the appearance of exclusive events associated with molecular subtypes, which have been extensively investigated to establish clinical management and the development of therapies targeted to this type of cancer. From a clinical aspect, the prognosis of the patient has focused on the characteristics of the index lesion (the largest focus in PCa); however, a significant percentage of patients (11%) also exhibit an aggressive secondary foci, which may determine the prognosis of the disease, and could be the determining factor of why, in different studies, the classification of the subtypes does not have an association with prognosis. Due to the aforementioned reasons, the analysis of molecular subtypes in several foci, from the same individual could assist in determining the association between clinical evolution and management of patients with PCa. Castration-resistant PCa (CRPC) has the worst prognosis and develops following androgen ablation therapy. Currently, there are two models to explain the development of CRPC: i) The selection model and ii) the adaptation model; both of which, have been found to include alterations described in the molecular subtypes, such as Enhancer of zeste 2 polycomb repressive complex 2 subunit overexpression, isocitrate dehydrogenase (NAPD+)1 and forkhead box A1 mutations, suggesting that the presence of specific molecular alterations could predict the development of CRPC. This type of analysis could lead to a biological understanding of PCa, to develop personalized medicine strategies, which could improve the response to treatment thus, avoiding the development of resistance. Therefore, the present review discusses the primary molecular factors, to which variable heterogeneity in PCa progress has been attributed.

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In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.

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INTRODUCTION: The aim of this article was to evaluate the effectiveness of the Gleason grade groups (GGG) system on a group of Argentinian patients with prostate cancer (PC) who underwent radical prostatectomy (RP). MATERIAL AND METHODS: We retrospectively studied 262 patients who underwent RP between 1996 and 2014. To determine the performance and validity of the GGG system, a Kaplan-Meier analysis and multivariate analysis with Cox proportional method were performed to evaluate biochemical recurrence, distance metastases and specific cancer mortality. The area under the curve (AUC) was calculated to compare new groups of degrees of the GGG system with the classical scheme of stratification into 3 groups. RESULTS: The median follow-up was 84 months. As the groups ascend, there is less confined organ disease (p <0.001) and greater extraprostatic extension (p <0.001), greater invasion of seminal vesicles (p <0.001) and greater lymph node involvement (p <0.001). The biochemical recurrence-free survival at 5 years was 68%, 55%, 22%, 9%, 0% of the 1-5 groups, respectively. Ten-years cancer-specific survival was 96%, 95%, 78%, 64%, 25% for group 1-5, respectively. In the multivariate analysis, the GGG system is presented as the only independent predictor of biochemical recurrence and specific cancer mortality. The AUC indicates that the GGG system has a higher prognostic discrimination compared to the classic 3-group system (6, 7, ≥8). CONCLUSIONS: The International Society of Urological Pathology (ISUP) GGG system is an independent predictor of biochemical recurrence and mortality from prostate cancer in patients treated with RP. The classification into 5 groups shows greater discrimination in the prognosis than the traditional Gleason classification.

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Prostate cancer (PCa) is one of the most prevalent male tumours. Stanniocalcin-1 (STC1) is a glycoprotein and, although the role of STC1 in human cancer is poorly understood, it is suggested to be involved in the development and progression of different neoplasms. This study investigated the protein expression profile of STC1 in PCa and benign prostatic hyperplasia (BPH) samples and STC1 signalling during cell proliferation and cell death in vitro using cell lines. We found higher levels of STC1 in PCa when compared to BPH tissue and that STC1 inhibited forskolin stimulation of cAMP in PC-3 cells. A monoclonal antibody against STC1 was effective in reducing cell proliferation, in promoting cell cycle arrest, and in increasing apoptosis in the same cells. Since STC1 acts as a regulator of prostatic tissue signalling, we suggest that this protein is a novel candidate biomarker for prostate tumour clinical progression and a potential therapeutic target.

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BACKGROUND: Several studies in the Caucasian population have shown that patients with Gleason 6 prostate cancer, based on surgical specimens, have low or no risk of metastasis. However, there is no data for men of African ancestry. The objective of this study was to estimate the overall, specific, and metastasis-free survival (MFS) of patients with a Gleason 6 score, based on the surgical specimen. PATIENTS AND METHODS: This was a monocentric retrospective study that included 723 consecutive patients treated by radical prostatectomy between 1 January 1 2000 and 31 March 2018, with a Gleason score of 6 based on the surgical specimen. Specific survival (SS) was defined as the time elapsed between surgery and death attributed to prostate cancer. Overall survival was defined as the time elapsed between surgery and death from all causes. The causes of death were verified in the medical records. Survival analyses without biochemical recurrence (BCR) and without salvage treatment were performed according to the Kaplan-Meier method. The Cox model was used for univariate and multivariate analyses. RESULTS: In total, 691 patients were included because 32 were excluded for missing data. Overall 5- and 10-year survival was 94.2% and 87.1%, respectively. SS and MFS were 100%, with a median follow-up of 8.5 years. The BCR rate was 16.5%, with a median time to BCR of 5.1 years. The frequency of salvage treatment was 13.0%, with a median time to surgery of 7.3 years. In univariate analysis, PSA, pathological stage, seminal vesicle invasion, positive margins, and lymph node dissection were significantly associated with an increased risk of BCR and salvage treatment, but only PSA and positive margins were significantly associated by multivariate analysis. DISCUSSION/CONCLUSION: No metastasis or disease-specific deaths were observed for men with Gleason score ≤6 prostate cancer at radical prostatectomy, in particular, men of African ancestry.

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The histology-based Gleason score (GS) of prostate cancer (PCa) tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide treatment strategies and patient management. The variability associated with PCa tumor sampling and the subjective determination of the GS are challenges that limit accurate diagnostication and prognostication. Thus, novel molecular signatures are needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, label-free LC-MS/MS proteomics is used to profile the proteome of 50 PCa tissues spanning five grade groups (n = 10 per group) relative to tissues from individuals with benign prostatic hyperplasia (BPH). Over 2000 proteins are identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. A panel of 11 prostate-derived proteins including IGKV3D-20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, and CTSZ display the potential to stratify patients from low and high PCa grade groups. Parallel reaction monitoring of the same sample cohort validate the differential expression of LMOD1, GYG1, IGKV3D-20, and RNASET2. The four proteins associated with low and high PCa grades reported here warrant further exploration as candidate biomarkers for PCa aggressiveness.

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PURPOSE OF REVIEW: The purpose of this review is to summarize the most current literature regarding the most important aspects to consider when developing a center of excellence for prostate imaging and biopsy. RECENT FINDINGS: Multiparametric MRI (mp-MRI) has changed the way we diagnose and treat prostate cancer. This imaging modality allows for more precise identification of areas suspicious in terms of harboring prostate cancer, enabling performance of targeted mp-MRI-guided biopsies that have been demonstrated to yield superior cancer detection rates. Centers worldwide are increasingly adopting this technology. However, obtaining results comparable with those findings published in the literature can be challenging. The imaging and biopsy process entails the need for a multidisciplinary team including a dedicated radiologist, urologist, and pathologist. Adequate mp-MRI interpretation for accurate lesion identification, acquaintance with the biopsy technique selected, and precise characterization of Gleason Score/Grade Groupings are equal determinants of accurate biopsy results. Furthermore, all specialists are required to attain appropriate learning curves to ensure optimal results. In this review, we characterize crucial aspects to consider when developing a center of excellence for prostate imaging and biopsy as well as insights regarding how to implement them.

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BACKGROUND: There are no comparative data on pathological predictors at diagnosis, between African Caribbean and Caucasian men with prostate cancer (PCa), in equal-access centers. The objective of this study was to evaluate the grade groups of an African Caribbean cohort, newly diagnosed with PCa on prostate biopsy, compared with a Caucasian French Metropolitan cohort. METHODS: A retrospective, a comparative study was conducted between 2008 and 2016 between the University Hospital of Martinique in the French Caribbean West Indies, and the Saint Joseph Hospital in Paris. Clinical, biological, and pathological data were collected at diagnosis. The primary outcome was the grade groups for Gleason score; the secondary outcome was the PCa detection rate. Multivariate analysis was performed using linear regression. RESULTS: Of the 1880 consecutive prostate biopsy performed in the African Caribbean cohort, 945 had a diagnosis of PCa (50.3%) and 500 of 945 in the French cohort (33.8%). African Caribbean patients were older (mean 68.5 vs 67.5 years; P = .028), had worse clinical stage (13.2% vs 5.2% cT3-4; P < .001) and higher median prostate-specific antigen (PSA) level (9.23 vs 8.32 ng/mL; P = .019). On univariate analysis, African Caribbean patients had worse pathological grade groups than French patients (P < .001). Nevertheless, after adjustment on age, stage, and PSA, there were no significant differences between the two cohorts (P = .903). CONCLUSION: African Caribbean patients presented higher PCa detection rate, and higher grade groups at diagnosis than French patients in equal-access centers on univariate analysis but not on multivariate analysis. African Caribbean patients with equivalent clinical and biological characteristics than Caucasian patients at diagnosis might expect the same prognosis for PCa.

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OBJECTIVE: Prostate cancer has a high prevalence and mortality, being the most diagnosed urologic cancer. Prostatic magnetic resonance imaging showed high sensitivity in the detection of clinically significant neoplasia and agreement with the Gleason score. Therefore, we attempted to evaluate the diagnostic accuracy of the prostate imaging reporting and data system, using biopsy and prostatectomy as the reference standard. The secondary goal of correlating prostatic magnetic resonance imaging findings and anatomopathological samples is obtained. MATERIALS AND METHODS: We retrospectively analyzed seventy-nine 1.5 Tesla prostatic magnetic resonance imaging scans in patients aged 31 to 86 years, performed at the Clinical Hospital of the Federal University of Paraná between January 2015 and February 2018. RESULTS: Considering all 79 patients, prostatic magnetic resonance imaging was able to diagnose tumor in 47 patients (59.4%). Considering the peripheral zone, the prostatic magnetic resonance imaging had a sensitivity of 75.0% (95% confidence interval: 52.1%-98.0%), specificity of 89.5% (95% confidence interval: 66.0%-100%), 94.4% positive predictive value (95% confidence interval: 71.0%-100%), 66.7% negative predictive value (95% confidence interval: 43.0%-69.0%), 83.8% Positive Likelihood Ratio (PVR) (95% confidence interval: 60.0%-100%), 27.9% Negative Likelihood Ratio (RVN) (95% confidence interval: 5.0%-50.0 %), and accuracy of 86.3% (95% confidence interval: 63.0%-100%). The receiver operating characteristic curve obtained demonstrated the sensitivity variation according to the prostate imaging reporting and data system score of the patients, obtaining an area under the curve of 84.8 for a prostate imaging reporting and data system cutoff of 3. CONCLUSION: The use of the prostate imaging reporting and data system score is useful for the screening and classification of prostate cancer, due to its easy reproducibility, even in a population with an unknown prostate cancer prevalence, which can be easily correlated with biopsy studies and/or radical prostatectomy.

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The human protein Polybromo-1 (PBMR1/BAF180) is a component of the SWI/SNF chromatin-remodeling complex that has been reported to be deregulated in tumors. However, its role in prostate cancer (PCa) is largely unknown. In this study, we described the PBRM1 transcriptional levels and the protein expression/localization in tissues of PCa patients and in prostatic cell lines. Increased PBRM1 mRNA levels were found in PCa samples, when compared to benign disease, and were correlated with higher Gleason score. We also verified that only the nuclear localization of PBRM1 protein is correlated with a more aggressive disease and high Prostate-Specific Antigen (PSA) levels in tissue microarrays. Intriguing expression patterns of mRNA and protein were identified in the cell lines. Although PBRM1 protein was restricted to the nuclei, in tumor cell lines in non-neoplastic cells, it was also present in vesicular-like structures that were dispersed within the cytoplasm. We knocked-down PBRM1 in the castration-resistant PCa (CRPC) cell line PC-3 and we verified that PBRM1 promotes the expression of several markers of aggressiveness, including EpCAM, TGF-ß, and N-Cadherin. Therefore, our data supported the hypothesis that PBRM1 displays a pivotal role in the promotion and maintenance of the malignant behavior of PCa, especially in CRPC.

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