Association of ARV7 expression with molecular and clinical characteristics in prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 109-109 ◽  
Author(s):  
Himanshu Joshi ◽  
Jacek K. Pinski
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Clinical Characteristics ◽  
Clinical Stage ◽  
Specific Antigen ◽  
The United States ◽  
Clinicopathological Parameters ◽  
Mesenchymal Transition ◽  
Regulatory Pathways ◽  
Custom Made

109 Background: Prostate cancer (PC) is the most common cancer in men over the age of 60 and the second leading cause of cancer mortality in the United States. Clinicopathological parameters such as Gleason score, tumor volume, surgical margins, prostate-specific antigen (PSA), Ki-67 index and clinical stage are used as prognostic markers for clinical outcomes. Identification of novel molecular markers could improve our understanding of the clinical behavior of this disease. Androgen receptor isoforms, in particular variant 7 (ARV7 or AR3) have been recently studied for elucidating their potential role in PC progression, associated with epithelial-mesenchymal transition (EMT), disease aggressiveness, increased proliferation and therapeutic resistance. Our study is analyzing the association of ARV7 mRNA expression to clinical characteristics and is analyzing the genomic data to identify differentially altered genes by ARV expression status, summarized as a potential functional network. Methods: We obtained the TCGA public dataset of prostate adenocarcinoma tumors (N=499) that included the clinical data, gene and isoform expression and mutation data. Cases were categorized into ARV7 over-expressing (ARV+) and normal or low expression (ARV –/N) by using a cut-off of upper 25th percentile of the background genomic expression. Analysis was performed in R and Perl by using custom-made scripts. Differentially altered genes and pathways were identified and were summarized as potential functional networks. Results: We categorized 30 out of the 499 tumors as ARV+. ARV7 over-expression was found to be significantly associated with older age at diagnosis (>70), advanced clinical stage, nodal involvement, high Gleason score and a poor therapeutic response. We also observed a trend towards shorter disease-free survival among ARV+ tumors. In addition, ARV+ tumors showed significantly higher number of mutations in 20 key regulatory pathways including Jak-STAT signaling, homologous recombination, ErbB and Wnt signaling pathways. Conclusions: ARV7 overexpression is associated with genomic alterations in key regulatory pathways and poorer clinical outcome in PC patients.

PSA-detected prostate cancer in the United States: A population-based study of 70,345 men with AJCC stage T1cN0M0 disease.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 50-50
Author(s):  
Hong Zhang ◽  
Lois B. Travis ◽  
Edward M. Messing ◽  
Ollivier Hyrien ◽  
Rui Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Prostate Cancer Screening ◽  
Specific Antigen ◽  
The United States ◽  
Population Based ◽  
Population Based Study ◽  
Ajcc Stage ◽  
High Risk Disease

50 Background: The U.S. Preventive Services Task Force (USPSTF) recently recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. This recommendation has heightened the debate about risks and benefits of prostate cancer screening, and underscored our limited understanding of PSA-detected prostate cancer. The purpose of this study was to determine the frequency of various risks of prostate cancer based on patient characteristics and PSA levels. Methods: This population-based study used the Surveillance, Epidemiology, and End Results (SEER) program to identify men with AJCC stage T1cN0M0 disease diagnosed between 1/2004 and 12/2008. Multivariate logistic regression was conducted to model the probability of developing low (PSA <10 mg/L and Gleason score ≤6), intermediate (PSA between 10 mg/L to 20 mg/L and/or Gleason score 7), and high risk diseases (PSA ≥20 mg/L, and/or Gleason score ≥8). Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were evaluated. Among them, 47.6%, 35.9% and16.5% had low, intermediate, or high risk disease, respectively. Odds ratios (OR) of having intermediate or high risk disease in patients ≥75 years old were 4.47 (95% confidence interval (CI) 3.81 to 5.26, p<0.01) and 9.39 (95% CI 7.25 to 12.16, p<0.01), respectively, when compared with patients aged <50. Also, black men had increased ORs for intermediate and high risk disease compared with white men (OR 1.50, 95% CI 1.42 to 1.58, p<0.01 for intermediate risk disease; OR 1.84, 95% CI 1.72 to 19.97, p<0.01 for high risk disease). While men aged >75 accounted for 11.8% of the population at risk, they accounted for 24.3% of intermediate and 26.1% of high risk disease. Conclusions: A substantial number of PSA-detected prostate cancer patients have either intermediate or high risk disease at diagnosis. Men age >75 or of black race have the highest risk of presenting with intermediate or high risk disease.

Diagnostic characteristics of men harboring lethal prostate cancer: A population-based analysis.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 217-217
Author(s):  
John Thomas Helgstrand ◽  
Nina Klemann ◽  
Birgitte Grønkaer Toft ◽  
Ben Vainer ◽  
Klaus Brasso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Clinical Characteristics ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Tumor Stage ◽  
Distant Metastatic Disease ◽  
Diagnostic Characteristics ◽  
Localized Disease

217 Background: Prostate specific antigen (PSA) based screening increases the number of men diagnosed with early localized prostate cancer (PCa). Further, curatively intended therapies have been demonstrated to reduce PCa mortality in randomized trials. However, controversy exists, and the overall impact on PCa mortality is less clear. Men who eventually die from PCa may constitute a subgroup with either adverse histopathological characteristics and/or clinically advanced disease at diagnosis. However, the clinical characteristics at diagnosis for men who eventually die from PCa are largely unknown. We retrieved clinical characteristics of all men dying from PCa in Denmark in an 18-year period. Methods: All men who died of PCa during the period 1995 to 2013 were identified in the Danish Causes of Death Registry. Age, Gleason score (GS), tumor stage classification, and PSA were retrieved from the Danish Prostate Cancer Registry (DaPCaR). For validation, manual revision of patient charts was performed. Patients were divided into three clinical phenotypes: distant metastatic disease, locally advanced/N+ disease, and localized disease. Patients with localized disease were further grouped according to GS and PSA. Results: A total of 19,487 men died of PCa in the period 1995-2013. In total, 46.7%, 16.8% and 25.1% of men presented with distant metastatic disease, locally advanced/N+ disease or localized disease, respectively. Among men with localized disease, 85.1% had GS ≥ 7 and only 2.1% (0.5% of all men dying from PCa) only, presented with low risk (PSA < 20 and GS ≤ 6) localized disease at the time of diagnosis. Conclusions: The majority of men (63.5%) who died from PCa had either locally advanced/N+ or M+ disease at diagnosis. Among men with localized PCa at diagnosis, the majority of men subsequently dying from PCa had either PSA > 20 ng/ml and/or adverse histopathological characteristics with Gleason score ≥ 7. A total of 94.5% of patients dying from PCa had either metastatic, locally advanced/N+, and/or GS ≥ 7 disease. Patients with localized disease, PSA < 20 ng/ml and GS ≤ 6 amounted for only 0.5% of all patients dying from PCa.

Pretreatment Nomogram for Prostate-Specific Antigen Recurrence After Radical Prostatectomy or External-Beam Radiation Therapy for Clinically Localized Prostate Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 168-168 ◽  
Author(s):  
Anthony V. D'Amico ◽  
Richard Whittington ◽  
S. Bruce Malkowicz ◽  
Julie Fondurulia ◽  
Ming-Hui Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Cox Regression ◽  
Clinical Stage ◽  
Specific Antigen ◽  
External Beam Radiation Therapy ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Psa Failure ◽  
Biopsy Gleason Score

PURPOSE: To present nomograms providing estimates of prostate-specific antigen (PSA) failure–free survival after radical prostatectomy (RP) or external-beam radiation therapy (RT) for men diagnosed during the PSA era with clinically localized disease. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine the prognostic significance of the pretreatment PSA level, 1992 American Joint Committee on Cancer (AJCC) clinical stage, and biopsy Gleason score in predicting the time to posttherapy PSA failure in 1,654 men with T1c,2 prostate cancer managed with either RP or RT. RESULTS: Pretherapy PSA, AJCC clinical stage, and biopsy Gleason score were independent predictors (P < .0001) of time to posttherapy PSA failure in patients managed with either RP or RT. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in the format of a nomogram stratified by the pretreatment PSA, AJCC clinical stage, biopsy Gleason score, and local treatment modality. CONCLUSION: Men at high risk (> 50%) for early (≤ 2 years) PSA failure could be identified on the basis of the type of local therapy received and the clinical information obtained as part of the routine work-up for localized prostate cancer. Selection of these men for trials evaluating adjuvant systemic and improved local therapies may be justified.

Critical analysis of the ability of the endorectal coil magnetic resonance imaging scan to predict pathologic stage, margin status, and postoperative prostate-specific antigen failure in patients with clinically organ-confined prostate cancer.

1996 ◽  
Vol 14 (6) ◽  
pp. 1770-1777 ◽  
Author(s):  
A V D'Amico ◽  
R Whittington ◽  
S B Malkowicz ◽  
D Schultz ◽  
M Schnall ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Prostate Cancer ◽  
Gleason Score ◽  
Clinical Stage ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Resonance Imaging ◽  
Endorectal Coil ◽  
Psa Failure ◽  
Biopsy Gleason Score

PURPOSE To determine whether there is a role for endorectal coil magnetic resonance imaging (erMRI) in the prediction of pathologic stage, margin status, and/or postoperative prostate-specific antigen (PSA) failure in patients with clinically organ-confined prostate cancer. PATIENTS AND METHODS Using erMRI, the radiologic-pathologic correlation of extracapsular extension (ECE) and seminal vesicle invasion (SVI) was evaluated in 445 surgically managed patients. Logistic regression multivariable analysis was applied to the clinical stage, PSA, biopsy Gleason grade, and erMRI findings to assess the outcomes of ECE, SVI, positive surgical margins (PSM), and postoperative PSA failure. RESULTS The accuracy of erMRI to predict for ECE and SVI numerically decreased with both increasing PSA and biopsy Gleason score because of the increasing false-negative scans in cases of microscopic transcapsular or seminal vesicle disease. Of patients who could not be categorized into low or high risk for postoperative PSA failure on the basis of clinical stage, preoperative PSA, and biopsy Gleason score, a negative or positive erMRI for ECE or SVI stratified these patients into groups with a 78% versus 21% (P < .0001) 3-year rate of actuarial freedom from PSA failure. In this subgroup, the overall accuracy of the erMRI was 70% +/- 6% and 94% +/- 2% for ECE and SVI, respectively. The most significant predictor on multivariable analysis of PSM was the erMRI finding of ECE (P = .0001). CONCLUSION This initial report suggests that a preoperative erMRI can identify clinically organ-confined prostate cancer patients at high risk for having ECE, SVI, and PSM that otherwise would be missed on the basis of the clinical stage, preoperative PSA, and biopsy Gleason score. Confirmatory studies are needed.

scholarly journals Correlation of focal neuroendocrine differentiation in prostate cancer with the parameters of predictive value

2019 ◽  
Vol 76 (11) ◽  
pp. 1115-1126 ◽  
Author(s):  
Milica Mijovic ◽  
Aleksandar Corac ◽  
Sonja Smiljic ◽  
Sladjana Savic ◽  
Predrag Mandic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Predictive Value ◽  
Tumor Volume ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Neuroendocrine Differentiation ◽  
Secretory Cells ◽  
Biopsy Material ◽  
Preoperative Serum

Background/Aim. Neuroendocrine (NE) cells are one of the epithelial populations in the prostate. It is well-known that the focal neuroendocrine differentiation (FNED) in prostate cancer (PC) is an aggressive subtype that most commonly evolves from preexisting PC which does not respond to hormone therapy (androgen independed PC). The incidence and clinical importance of FNED in PC is not clearly understood because of conflicting results in the studies, and evaluation of FNED is not routinely performed in clinical practice. The aim of the present study is to determine the importance of FNED presence in the examined prostate changes with special reference to the relationship of FNED degree in PC with some parameters of predictive value [Gleason score, preoperative serum total prostata specific antigen (PSA) value, tumor volume and tumor stage]. Methods. The study included the biopsy material from 100 untreated consecutive prostate pathological changes: 70 PC, 20 prostatic intraepithelial neoplasia (PIN) and 10 benign prostatic hyperplasia (BPH). The patients with PIN and BPH were the control groups. A block containing part of the main bulk of pathological change was chosen as representative based on hematoxylin-eosin appearance, and a section of this block was immunohistochemically stained for the tissue PSA (to mark prostatic secretory cells) and chromogranin A, serotonin and synaptophysin (to mark NE cells). Results. We found a very pronounced degree of FNED differentiation in 16 (22.9%) PC. Ten (62.5%) of them had Gleason score ? 7, the average serum PSA level was 32.62 ? 30.80 ng/mL, average tumor volume was 43.18 ? 31.45 mL and 6 (37.5%) of this PC were detected in D clinical stage with distant hematogenous metastases. The FNED is negatively correlated with the serum PSA level, Gleason score and clinical stage positively correlated with the tumor volume, but without statistically significant differences. Conclusion. The FNED has no significant role in the prognosis of PC.

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