Gleason Score Research Articles

Prognostic Significance of Cribriform Architecture of Pattern 4 Prostatic Adenocarcinomas

Objective: Among prostate cancer patients, the Gleason score is associated with adverse clinical outcomes. We aimed to determine whether cribriform architecture in prostate cancer patients without a history of treatment was related to prognosis in patients with Gleason pattern 4 of prostate cancer.  Material and Methods: A prospective cross-sectional study included (n=450) consecutive prostate biopsy specimens between June 2014 and May 2015, out of which (n=237) had pattern 4 prostate adenocarcinoma. Demographic, clinical, and follow-up details were obtained. Patients (n = 86) with a treatment history were excluded from the study.  Results: Univariate Cox regression analysis of diagnostic biopsies from (n=151) patients with pattern 4 of prostate cancer who had been followed for an average of 70.3 months demonstrated that the cribriform architecture of prostate cancer with pattern 4 was independently associated with poorer disease-specific survival in biopsies with a hazard ratio (HR) of 3.1, 95% Confidence Interval (CI) of 0.9-10.6, and P value of <0.001.  Conclusion: It is concluded that a cribriform architecture of prostate cancer in biopsies with pattern 4 adenocarcinoma is associated with a lower disease- specific survival rate. Therefore, it is essential to report the presence and percentage of cribriform architecture in patients with pattern 4 prostate cancer.

Focal Unspecific Bone Uptake on [18F]PSMA-1007 PET: Evaluation Analog PROMISE Criteria and Validation via PET/CT Follow-Up.

Background: Focal unspecific bone uptake (UBU) is common in [18F]PSMA-1007 PET/CT, yet its clinical significance remains unclear, causing uncertainty in treatment decisions. Material and Methods: We retrospectively analyzed 99 prostate cancer patients (age 69 ± 7) who underwent [18F]PSMA-1007 PET/CT scans (3 MBq/kg; uptake time 70 ± 14 min) for staging and follow-up (after 13.0 ± 7.2 months). Semiquantitative assessment using the miPSMA score, analogous to the PROMISE criteria, evaluated the prevalence of UBU and bone metastases. Results: In the initial PET/CT scan, 56 patients had 230 lesions classified as UBU. A total of 19 patients were found to have bone metastases and UBU, while 24 patients had no focal bone uptake. UBU distribution was as follows: ribs (50%), spine (30%), pelvis (15%), and other sites (5%). There were no significant differences in age, Gleason score, injected tracer dose, uptake time, SUVpeak of UBU, or SUVmean in the spleen and parotid gland between patients with and without UBU. Follow-up showed stable miPSMA-score and CT appearance in 44/56 patients with UBU (79%), minor changes in 5/56 patients (8%), and new bone metastases in 7/56 patients (12%). Patient-specific analysis indicated at least one bone metastasis initially classified as UBU in 3/56 patients (5%) and new bone metastases in 4/56 patients (7%). In total, 4 of the 24 patients (17%) without initial focal uptake developed osseous metastases at follow-up. Conclusions: No significant differences were found between patients with or without UBU. Only a small portion of UBU (2%) evolved into metastases, a lower rate than the development of new osseous metastases, which appears to be independent of UBU.

Enhancing Prostate Cancer Staging: Association of 68Ga-PSMA PET/CT Imaging with Histopathological Grading in Treatment-Naive Patients.

This study aimed to evaluate the correlation between 68Ga-PSMA uptake in PSMA PET/CT in primary prostate cancer (PC) and its histopathological grading (Gleason score and ISUP grade). Additionally, we compared preoperative biopsy histopathological findings with definitive pathology results in radical prostatectomy (RP) specimens. We retrospectively analyzed 86 patients who underwent 68Ga-PSMA PET/CT for primary PC staging, of which 40 patients later underwent radical prostatectomy. PET/CT results, including SUVmax values, were correlated with GS and PSA concentrations. Histopathology reports were analyzed and compared between biopsy and final pathology results following RP. A significant positive correlation was observed between SUVmax and ISUP grades (Pearson's ρ = 0.34, p < 0.001), with higher SUVmax values associated with more advanced grades. A cut-off SUVmax value of 5.64 was determined to predict upstaging in patients, yielding a sensitivity of 76% and a specificity of 60% (AUC = 0.82, 95% CI: 0.70-0.94). Additionally, 57.5% of patients experienced a grade shift following RP, with a 35% upgrade and 22.5% downgrade in ISUP grades. 68Ga-PSMA PET/CT demonstrated high sensitivity in detecting high-risk prostate cancer, particularly in patients with GS > 7 or PSA levels ≥ 10 ng/mL. The findings suggest that this imaging modality may be less effective for the staging of patients with lower GS or PSA values, that is, low-risk PCa. Further prospective studies are necessary to validate these results.

Clinical Factors Associated With Suspicious 18F-DCFPyL PSMA PET Activity in Patients Initially Managed With Radical Prostatectomy Including Prostate-Specific Antigen < 0.5 ng/mL.

There are limited data on PSMA PET/CT for workup of recurrence after radical prostatectomy (RP) at low PSA values. We evaluated a PSMA PET/CT cohort of patients with post-RP, focusing on patients with PSA < 0.5 ng/mL. We identified a retrospective cohort who underwent piflufolastat F-18 PSMA PET/CT across an 11 hospital system from July 2021 to February 2023. Prostate-specific membrane antigen (PSMA) positivity was determined by radiology reports. Univariable and multivariable logistic regression identified factors associated with suspicious PSMA activity. Median PSA was 0.37 ng/mL (IQR, 0.15-1.29 ng/mL), with 49% of patients overall having at least 1 suspicious PSMA-avid lesion. Rates of scan positivity among patients with PSA < 0.2 and 0.2 to 0.5 ng/mL were 34% and 38%, respectively. Among all patients, 25% (104/415) had pelvic disease (prostate bed or N1) and 24% (100/415) had M1 disease. Among patients with PSA < 0.5 ng/mL, prior postoperative radiation was associated with suspicious PSMA activity. In the overall cohort, age, PSA at PSMA PET/CT, and RP Gleason grade were associated with PSMA positivity. PSADT, EAU risk, and CAPRA-S were all associated with suspicious PSMA activity. Over one-third of patients with PSAs < 0.2 ng/mL had imaging findings concerning for recurrence. Prior postoperative radiation was associated with higher rates of PSMA positivity among patients with PSA < 0.5 ng/mL, and half of patients with evidence of PSMA avid distant metastatic disease underwent metastasis-directed therapy. PET-PSMA imaging at low PSAs can be considered to inform salvage therapies.

Androgen deprivation therapy, neoadjuvant androgen deprivation therapy, and adjuvant androgen deprivation therapy in patients with locally advanced prostate cancer: a multi-center real-world retrospective study.

Determining the potential benefit of neoadjuvant androgen deprivation therapy (ADT) and adjuvant ADT in patients with locally advanced prostate cancer (LAPC) undergoing complete resection. 139 patients diagnosed with cT3-4, or cN+ LAPC in Xiangya Hospital and The First Affiliated Hospital of University of South China from 2010 to 2021 were collected. Cancer-specific survival (CSS) and overall survival (OS) of patients were assessed using Kaplan-Meier and Cox proportional risk analysis. We also analyzed the functional outcomes of two subgroups of patients who underwent radical prostatectomy (RP). Of the 182 patients with cT3-4, or cN+ LAPC, 139 patients (76.4%) were enrolled in the study with a 5-year survival rate of 82.3%. 45 patients (32.4%) received ADT alone, 46 patients (33.1%) received neoadjuvant ADT before surgery, and the remaining 48 patients (34.5%) received surgery with adjuvant ADT. Neoadjuvant ADT before surgery and surgery with adjuvant ADT were associated with significantly improved survival compared with ADT alone. Multivariate Cox models showed that neoadjuvant ADT before surgery (hazard ratio [HR], 0.29; 95% CI 0.13-0.92) or surgery with adjuvant ADT (HR, 0.26; 95% CI 0.16-0.78) was associated with improved CSS compared with ADT alone. Regional lymph node metastasis, positive lymphovascular invasion, and Gleason score 9 + were independent predictors of LAPC CSS and OS. More patients in the neoadjuvant ADT before surgery group achieved final continence status within 12 months after surgery (93.48% v 77.08%). CSS and OS were significantly prolonged in cT3-4, or cN+ LAPC patients who received neoadjuvant ADT before surgery and surgery with adjuvant ADT compared to ADT alone.

Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer

BackgroundWhether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.MethodsWe conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.ResultsA total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P=0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P=0.94).ConclusionsFive-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.)

Application of a Modified SegFormer Architecture for Gleason Pattern Segmentation

A key element of morphological assessment in prostate cancer (PCa) diagnostics is the Gleason score, which is based on the architecture of tumor growth in biopsy or prostatectomy samples. During this process, biopsies from the prostate's pathological areas are evaluated to identify the most common and severe architectural patterns (referred to as Gleason patterns), each of which is assigned a score in the Gleason grading system. The resulting total score serves as a critical predictor for disease progression and metastasis. This research focuses on enhancing the efficiency of morphological examination in PCa by utilizing automatic segmentation of Gleason patterns in whole slide images (WSI) in *.svs format, with 40x magnification and an average spatial resolution of 0.258 microns per pixel. Segmentation was performed using a neural network with a SegFormer architecture, supplemented by an EdgeNeXt (small variant) subnet. The proposed solution successfully identified Gleason patterns of grades 3, 4, and 5. The best model performance for detecting combined Gleason patterns 3, 4, 5, and 4, 5 was achieved with input images sized 512x512 (tile size) and a batch size of 8, resulting in an F-score of 0.835 and 0.769, respectively.

Predicting Metastasis and Mortality Risk in Prostate biopsy using genomics and biopsy related factors

Abstract Introduction/Objective Prostate cancer, the most prevalent cancer among men, is diagnosed through biopsy, yet its predictive accuracy for metastasis and mortality risk remains limited. An approach to stratifying this risk is by combining biopsy data and genetics. The Decipher genomic classifier aids in estimating such risks. This study investigates the correlation between Decipher, biopsy-related factors, and the risk of prostate cancer metastasis or mortality. Methods/Case Report 50 prostatic adenocarcinoma biopsies were analyzed. Patient age, average tumor volume in positive cores, PSA levels, and Gleason score were documented. Employing Tobit regression with maximum likelihood estimation, the study examined the link between various factors and metastasis/mortality risk of prostatic cancer. Dependent variables encompassed 5, 10, and 15-year risks, while the independent variable was patient age, positive to total core ratio, average tumor volume in positive cores, PSA level, and grade group of the prostate cancer. The model integrated three dummy variables-Grade Group 1, 3, and 4, with Grade Group 2 as reference. Coefficients gauged the distinct impact of Level 1, 3, and 4 diagnoses on outcomes relative to Level 2. Statistical significance was tested conventionally. Results (if a Case Study enter NA) Grade Group 1 (Gleason score: 3 + 3): 2.35 percentage point increase in the risk of metastasis within 10 years. 3.51 percentage point increase in the risk of mortality within 15 years. Grade Group 2 Base level for comparison with other grade groups. Grade Group 3 (Gleason score: 4 + 3): No statistically significant difference in the predicting 5 or 10 year risk of metastasis compared to Grade Group 2. No statistically significant difference in the predicting 15 year risk of mortality compared to Grade Group 2. Grade Group 4 (Gleason score: 4 + 4): 10.07 percentage point increase in the risk of metastasis within 5 years. 17.27 percentage point increase in the risk of metastasis within 10 years. 18.48 percentage point increase in the risk of mortality within 15 years. Conclusion The findings suggest combining genomics and grade group can help predict the risk of metastasis and mortality in prostate biopsy. Grade Group 4 diagnosis greatly impacts metastasis and mortality in all timeframes.While Grade Group 1 has a smaller but still significant impact on the 10 and 15 year risk of metastasis and mortality. However, Grade Group 3 diagnosis does not significantly impact the risk of metastasis in any of the timeframes considered.

Enhancing Early Detection of Prostate Cancer Using PSA-Guided Screening in High-Risk Men Under 50

Abstract Background Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer. Methods This retrospective analysis utilized data from our hospital’s prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race. Results In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision. Conclusion Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.

Weakly supervised deep learning for diagnosis of prostate cancer after radical prostatectomy: a population- based, multicenter study

Abstract Introduction/Objective The pathological diagnosis of prostate cancer after radical prostatectomy (RP) is a challenging and time-consuming process. Artificial intelligence has the potential to enhance this situation significantly. Our study aimed to assess the efficacy of weakly supervised deep learning, specifically focusing on practical diagnostic tasks for RP specimens. Methods/Case Report We obtained slices from clinical centers across four regions in China. The model was developed based on a multiple instance learning framework. We evaluated the model’s predictive accuracy, covering both slice-level and lesion-level diagnoses. Additionally, we investigated lesion localization using attention visualization. Slice-level diagnosis included prostate cancer detection and Gleason grading, while lesion-level diagnosis involved recognizing index lesions and non-index lesions. Results (if a Case Study enter NA) The study involved 13,245 slides from 304 patients. The area under the curve values in four validation sets ranged from 0.921 (95% CI 0.913–0.930) to 0.964 (95% CI 0.959–0.968). Regarding Gleason grading, the model demonstrated quadratic Weighted Kappa values of 0.748 and 0.720 for internal and external validation, respectively. The model predicted 1,683 (35.3%) positive and 3,081 (64.7%) negative slices in all validation sets. The median area of index lesions and non-index lesions was 92.6mm2 (IQR: 54.2–130.0mm2) and 3.5mm2 (IQR: 1.4–10.9mm2) (p&amp;lt;0.001), respectively. The model accurately predicted index lesions in all cases for three validation sets. Furthermore, the model achieved 100% accuracy in predicting slides with the maximum tumor area for index lesions in two validation sets. In visual assessment, 200 randomly selected slices predicted as true positive demonstrated that the model could identify 97.5% (195/200) of the index lesions. Conclusion The weakly supervised deep learning model demonstrated remarkably high diagnostic and localization capabilities in identifying index lesions within RP specimens. This targeted approach would effectively alleviate the diagnostic workload associated with pathology assessments for prostate cancer.

Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review.

Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma. Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses. In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05). Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.

Comparative Study of Gleason 7 (3+4) and (4+3) Prostatic Adenocarcinomas with Prog-nostic Criteria and Immunohistochemical Profiles of AMACR, PSA and Ki-67.

To compare Gleason 7 (3+4) and (4+3) prostatic adenocarcinoma (PC) with different prognostic criteria through immunohistochemical analysis with anti-PSA, anti-Ki 67 and anti-AMARC antibodies. We analyzed 221 surgical specimens from patients between 40 and 86 years-old (mean=63) with PC. The immunohistochemical study was performed with anti-PSA, anti-Ki 67 and anti-AMARC. The microscopic fields were photographed with an Olympus DP70 digital camera coupled to an Olympus BX51 microscope and archived in TIFF. Proportion and intensity criteria were used to quantify the anti-PSA antibody and for the anti-Ki 67 antibody, the quantification by similarity of this antibody in breast carcinomas. Anti-AMACR protein expression was based on four scores: negative, weak, moderate and strong. The statistical analysis was performed with the Graph Pad Prism 5 program. In the Gleason score 7 (3+4) we had 91.72% in pT2 and 8.27% in the pT3 group; 8.27% recurrences, of which 90.90% in the pT2 group. In the Gleason score 7 (4+3) we had 77.27% in the pT2 group and 22.72% in the pT3 group and 10.22% of relapses, of which 66.66% in the pT2 group and 33.33% in the pT3 group. In 6.81% of cases there was an increase in the anti-Ki 67 index and in 2.27% of the cases, there was an increase in the immunoexpression of anti-p53 when comparing Gleason score 7 (3+4) with Gleason score 7 (4+3). Our study confirmed differences in the Gleason score 7 (3+4) and Gleason score 7 (4+3) of PC when comparing prognostic criteria. Anti-Ki 67 and anti-PSA antibody immunostaining showed a positive correlation as the Gleason score 7 increased from (3+4) to (4+3).

Targeted Biopsy Is Sufficient for Men on Active Surveillance for Early-Stage Prostate Cancer.

Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. mpMRI targeting has become a standard. It is unclear whether targeted biopsy alone reliably identifies the dominant lesion, thereby obviating the need for systematic sampling. Participants enrolled in AS with early-stage prostate cancer (PSA < 20, cT1-2, GG1-2) and underwent 2+ systematic biopsy sessions with or without MR-targeted sampling. The findings for dominant Gleason Grade (GG) and tumor localization were assessed. Among 821 men who underwent MR fusion biopsies, 82% were diagnosed with GG1 and 18% with GG2. Sixty-two percent had their first MR fusion biopsy as diagnostic or confirmatory. Across all fusion biopsies, MRI-targeted detection of GG and/or tumor location overlapped with systematic sampling for 95% of cases. For 5% of cases, systematic biopsy was unique in detecting GG and location outside the target. Most unique lesions detected outside the target had marginally aggressive features: 73% GG2 of low-volume and favorable histologic subtypes. In men with MR fusion biopsies, targeting alone identified the dominant GG and location most of the time (95%); 25% of dominant lesions were contiguous to the target, suggesting that better sampling of the target improves detection. The remaining 5% of men had higher-grade, low-volume disease outside the targeted lesion of which only 2% had aggressive risk features. MR fusion targeting, without systematic sampling, may be sufficient to monitor men on AS. Few high-risk cancers are missed, all of limited volume and favorable histology.

Prognostic Outcomes and Predictive Factors in Non-Metastatic Castration-Resistant Prostate Cancer Patients Not Treated with Second-Generation Antiandrogens.

Background/Objectives: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and high-risk features frequently have progression to life-threatening metastasis without second-generation antiandrogens. This study investigated nmCRPC patients for the survival and prognostic factors from a cohort before the approved use of second-generation antiandrogens. Methods: From March 2016 to January 2021, 326 patients treated with second-generation antiandrogens for metastatic castration-resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer were retrieved. Forty-four patients experiencing nmCRPC with no use of second-generation antiandrogens were reviewed. The prognostic factors, at initial diagnosis or at nmCRPC, associated with metastasis-free survival (MFS) and overall survival (OS) were analyzed. Results: The median follow-up time after nmCRPC was 46 months. The median PSA level at nmCRPC was 2.7 ng/mL. Thirty-eight of forty-four patients with nmCRPC had a PSA doubling time (PSADT) of 10 months or shorter, and the median PSADT was 4 months. The median OS from nmCRPC was 53 months, and the median interval for nmCRPC patients progressing to mCRPC was 20 months. Upon univariate analysis, PSADT < 10 months (p = 0.049) and the very-high-risk group at the initial diagnosis (p = 0.043) were associated with significantly shorter post-nmCRPC MFS. The very-high-risk group (p = 0.031) was associated with significantly worse post-nmCRPC OS. In terms of survivals from the initial diagnosis of prostate cancer, Gleason grade ≥ 8 was the only independent factor with MFS and OS. Conclusions: Without second-generation antiandrogens, nmCRPC patients with PSADT <10 months and in the initial very-high-risk group developed subsequent mCRPC in a significantly faster fashion. Patients of the very-high-risk group had shorter survival rates after nmCRPC.

ANALYSIS OF CD10 EXPRESSION IN PROSTATE ADENOCARCINOMA AND ITS CORRELATION WITH DIFFERENT CLINICOPATHOLOGICAL PARAMETERS AT RNTMC, UDAIPUR

Objective: The study aimed to analyze the expression of CD10 in prostate adenocarcinoma to aid in early diagnosis and anti-CD10 targeted therapy. Methods: This was a cross-sectional study conducted in the Histopathology section of the Department of Pathologyat RNTMC, Udaipur, after approval from the ethical committee and institutional review board. This study was conducted on 92 patients suspected to have prostate cancer. The cases were assessed for Gleason score, Gleason Grade, and Serum Prostate Specific Antigen (PSA) levels. We performed IHC detection of CD10 in prostatic specimens and correlated the various patterns of CD10 expression concerning histopathological diagnosis. Results: In our study, we found membranous expression in low-grade carcinomas with low Gleason score and grade. The high-grade carcinomas with high Gleason score and Grade predominantly showed cytoplasmic expression. The increased CD10 cytoplasmic expression was correlated with serum PSA level. Conclusion: In our study, CD10 was found to be relevant. The low-grade carcinomas showed membranous positivity and high-grade carcinomas showed cytoplasmic expression. One hypothesis states that cytoplasmic expression is due to the localization of CD10 in the cytoplasm. Our study favors this hypothesis as there is cytoplasmic expression in high-grade tumors. In the future, this could be used as a diagnostic marker.

NFYA-mediated promotion of castration-resistant prostate cancer progression through EGR4 regulation

This research investigates the intricate involvement of nuclear Transcription Factor Y Subunit Alpha (NFYA) in the advancement of castration-resistant prostate cancer (CRPC) and its consequential impact on early Growth Response 4 (EGR4) expression. NFYA demonstrates a significant elevation in CRPC tissues and cell lines, displaying robust upregulation in metastatic prostate cancer (mPCa) samples, closely associated with the Gleason score. Immunohistochemistry validates heightened nuclear staining of NFYA in CRPC patients, highlighting its crucial role in the progression of advanced prostate cancer. Silencing NFYA through siRNA in androgen-independent cell lines markedly impedes cell growth and migration, emphasizing NFYA’s pivotal role in promoting CRPC behavior. RNA-seq analysis identifies EGR4 as a downstream target of NFYA, with both genes consistently upregulated in CRPC. Validating this finding, heightened expression of EGR4 is observed in CRPC samples. In vivo studies utilizing a mouse model demonstrate that NFYA silencing substantially inhibits LNCaP-AI/22RV1shNFYA xenograft tumor growth, accompanied by reduced expression of EGR4 and Ki67. This comprehensive study reveals the multifaceted role of NFYA in CRPC progression, elucidates its downstream impact on EGR4, and underscores the therapeutic potential of targeting NFYA to inhibit CRPC growth in vivo. These findings contribute valuable insights into potential therapeutic strategies for managing CRPC.

12234 Gα13 Promotes Clonogenic Growth By Increasing Tolerance To Oxidative Metabolic Stress In Prostate Cancer Cells

Abstract Disclosure: D. Wu: None. W. Lim: None. X. Chai: None. V.P. Seshachalam: None. S.A. Rasheed: None. S. Ghosh: None. P.J. Casey: None. Gα13 and Gα12 are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors. Analyses of tumor specimens indicate that Gα13 expression correlates with patient survival in several solid cancers. We previously reported a role for Gα13 in cell migration and invasion in prostate cancer cell lines. Interestingly, patient data supports the notion that mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason scores. Gα13 lower-expressing LNCaP cells also have lower SOD2 protein levels compared to the Gα13 higher-expressing PC3 cells. Hence, we explored the role of Gα13 in prostate tumorigenesis, and its effect on cellular processes such as cell survival and mitochondrial metabolism, in human prostate cancer cell lines PC3 and LNCaP. We stably knocked-down GNA13 expression in PC3 cells and overexpressed GNA13 in LNCaP cells. We found that Gα13 promoted anchorage-independent cell growth in PC3 and LNCaP cell lines, as assessed by soft agar colony formation, spheroid formation, and xenograft tumor growth. Whole-genome transcriptome analyses suggested that Gα13-regulated genes are functionally enriched in the mitochondria compartment and that GNA13 expression positively correlated to SOD2 transcript levels in PC3 cells. We found that silencing GNA13 sensitized PC3 cells to long-term oxidative metabolic stress when cultured in media containing non-glycolytic metabolites, namely galactose, glutamate plus malate, and succinate. Furthermore, Gα13 levels impacted the abundance of SOD2 protein in the mitochondria, as well as SOD2 promoter activity and mRNA expression. In addition, silencing GNA13 increased mitochondrial superoxide levels in PC3 cells when cultured in galactose medium, as assessed by MitoSOX staining and flow cytometry. Moreover, overexpression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent cell growth in PC3 cells. Importantly, anchorage-independent cell growth was not rescued when a catalytically-inactive SOD2(Q167A) mutant was expressed. Likewise, stable knockdown of SOD2 suppressed the effect of overexpression of Gα13 on anchorage-independent cell growth in LNCaP cells. We propose a novel biological route of Gα13-mediated anchorage-independent growth and response to oxidative metabolic stress through regulation of SOD2 expression in prostate cancer cells. Given that SOD2 protein levels correlate with prostate cancer Gleason grade, identifying the upregulated GPCRs that signal through Gα13 in prostate cancer could lead to novel preventive or therapeutic strategies. Presentation: 6/1/2024

Serum ACSL4 levels in prostate cancer patients and its relationship between patient prognosis: A prospective observational study.

In this prospective observational study, our objective was to investigate the serum levels of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in prostate cancer (PCa) patients and examine its association with other serum biomarkers, and the clinical outcomes of PCa patients. This prospective observational study was conducted from January 2019 to October 2021, including 103 cases of PCa patients and 101 cases of benign prostate hyperplasia (BPH) patients who received treatment at our hospital. All patients had their serum ACSL4 levels measured using enzyme-linked immunosorbent assay before treatment. The clinical outcomes included age, body mass index, gender, systolic blood pressure, diastolic blood pressure, tumor node metastasis stage, Gleason scores, and prostate volume and serum biomarkers were collected. All patients were followed up for 36 months, the overall survival and disease-free survival were recorded for all patients. All data used SPSS 26.0 for analysis. The phosphorus (P) and serum low-density lipoprotein cholesterol levels were significantly higher in PCa patients compared to BPH patients. Furthermore, compared to the BPH patients, the serum ACSL4 and free prostate-specific antigen levels were significantly decreased while serum total prostate-specific antigen (tPSA) levels were significantly elevated in PCa patients. Pearson correlation analysis showed a positive correlation between ACSL4 levels and free prostate-specific antigen levels, while a negative correlation was observed with P and tPSA levels. ACSL4 might serve as a biomarker for diagnosing PCa with the AUC was 0.747, cutoff value of 33.68 ng/mL, sensitivity of 70.3%, and specificity of 60.2%. Finally, we found that ACSL4, tPSA, and P were identified as risk factors associated with PCa patients. Our findings indicated that the serum levels of ACSL4 were significantly decreased in PCa patients compared to BPH patients. Serum ACSL4 could be used as a potential biomarker for early PCa diagnosis and prognosis.

Histopathological Study Of Prostate Cancer According To Gleason Score

The aim of this study was to histopathological alternation prostate cancer according Gleason systems . The total number of study samples was (60 ) that taken from men who suffered prostate cancer .patients diagnosed by a specialist doctor. Blood samples taken from all groups for estimation of levels of PSA. Second type of samples was biopsy and paraffin block that taken from PC patients for detection of histopathological alternations depending Gleason score. The result obtained from histopathology method that the prostate cancer in early stage poorly differentiated gland to loss gland formation in advanced early stage.

B-321 Enhancing Early Detection of Prostate Cancer Using PSA-Guided Screening in High-Risk Men Under 50

Abstract Background Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer. Methods This retrospective analysis utilized data from our hospital's prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race. Results In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision. Conclusions Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.