The Association of Gleason Score and Tumor Stage in the Prevalence of DNA Repair Gene Mutations in Localized Prostate Cancer

To speak with Bob Dylan, ‘’..times they are a changing..’’, particularly when it comes to our insight in the genetic changes in prostate cancer. In the early days of molecular genetics studies of prostate cancer, scientists often referred to prostate cancer as being very different from other cancers, e.g. mutations in TP53 were rarely found in this malignancy. With the large scale introduction of next-generation sequencing and the impressive SU2C initiative, focusing on metastatic/advanced cancers, it was shown that prostate cancer was not that of a ‘’cancer genetic outlier’’. TP53-, Rb mutations ánd a rather high frequency of aberrations in genes encoding DNA repair proteins were found in advanced prostate cancer (metastatic CRPC).

A straight forward hypothesis is that these mutations have prognostic significance, i.e. mutations in pivotal cancer pathways are associated with clinical-, pathological stage, and grade, which in turn are a good proxy/surrogate for the outcome of the disease. Marshall and colleagues1 focussed on DNA repair gene mutations and ‘mined’ existing DNA sequencing information (TCGA, NatureGenetics via cBioportal) to test this hypothesis. There appeared to be a clear correlation between pathological stage (pT3/4 versus pT2) and Gleason Grade groups (GG ≥ 3 versus GG 1-2). In the cT≥3 ánd GG ≥3 tumors in >20% DNA repair gene mutations were identified. Interestingly there appeared

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stephen j freedland

Stephen J. Freedland, MD

Stephen J. Freedland, MD, is director of the Center for Integrated Research in Cancer and Lifestyle and co-director of the Cancer Genetics and Prevention Program and Associate Director for Faculty Development at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. He is also a faculty physician in the Division of Urology within the Department of Surgery at Cedars-Sinai. He has served on numerous American Urological Association guideline panels for prostate cancer and co-chaired a prostate cancer guideline panel for the American Society of Clinical Oncology.

Dr. Freedland's clinical area of expertise focuses on urological diseases, particularly benign prostatic hyperplasia and prostate cancer. His approach toward cancer prevention and awareness focuses on treating the whole patient, not just the disease, by combining traditional Western medicine with complementary holistic interventions. His research interests include investigations on urological diseases and the role of diet, lifestyle and obesity in prostate cancer development and progression, as well as prostate cancer among racial groups and risk stratification for men with prostate cancer.


PCAN: October 2018

The Use of PET/CT in Prostate Cancer - Full Text Article

Background: Positron emission tomography/computed tomography (PET/CT) has recently emerged as a promising diagnostic imaging platform for prostate cancer. Several radiolabelled tracers have demonstrated efficacy for cancer detection in various clinical settings. In this review, we aim to illustrate the diverse use of PET/CT with different tracers for the detection of prostate cancer.
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PCAN: September 2018

Correlation of B7-H3 with Androgen Receptor, Immune Pathways and Poor Outcome in Prostate Cancer: An Expression-based Analysis – Full Text Article

BACKGROUND: B7-H3 (CD276), part of the B7 superfamily of immune checkpoint molecules, has been shown to have an immunomodulatory role. Its regulation, receptor and mechanism of action remain unclear. B7-H3 protein expression correlates with prostate cancer outcomes, and humanized monoclonal antibodies (that is, enoblituzumab) are currently being investigated for therapeutic use. Here we used genomic expression data to examine the relationship between B7-H3 mRNA expression and prostate cancer.
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PCAN: August 2018

Longitudinal Assessment of Urinary PCA3 for Predicting Prostate Cancer Grade Reclassification in Favorable-Risk Men During Active Surveillance - Full Text Article

BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS).

METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate magnetic resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ⩾3 years of monitoring were included. The utility of first PCA3
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PCAN: July 2018

Comparison of Multiparametric Magnetic Resonance Imaging and PSMA PET/CT to Prostatectomy Histopathology - Full Text Article

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however, guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology.
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PCAN: June 2018

Periprostatic Adipose Inflammation is Associated with High-Grade Prostate Cancer - Full Text Article

Background: Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown.

Methods: In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives
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PCAN: May 2018

Post Prostatectomy Outcomes of Patients with High-risk Prostate Cancer Treated with Neoadjuvant Androgen Blockade - Full Text Article

Background: Patients with high-risk prostate cancer have an increased likelihood of experiencing a relapse following radical prostatectomy (RP). We previously conducted three neoadjuvant androgen-deprivation therapy (ADT) trials prior to RP in unfavorable intermediate and high-risk disease.

Methods: In this analysis, we report on the post-RP outcomes of a subset of patients enrolled in these studies. We conducted a pooled analysis of patients with available follow-up data treated on three neoadjuvant trials at three institutions. All patients received intense ADT prior to RP. The primary endpoint
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