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ERG protein expression and gene rearrangements are present at lower rates in metastatic and locally advanced castration-resistant prostate cancer compared to localized disease.

By:
Contributors: Bryan Donnelly, MD, MSc, FRCSC, Kiril Trpkov, MD, FRCPC, Tarek Bismar Research Group
Urology. 2013 Aug;82(2):394-9. doi: 10.1016/j.urology.2013.03.029. Epub 2013 Jun 6.

Abstract

 

OBJECTIVE:

To compare ERG expression and gene rearrangements rates in metastatic and castrationresistant prostate cancer (CRPC) to localized disease as ERG is the most common genetic event in early prostate cancer (PCa) with potential prognostic and therapeutic implications.

METHODS:

We evaluated ERG protein expression in 344 patients with PCa in 3 cohorts including localized, metastatic, and castrationresistant disease using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

RESULTS:

ERG protein expression was detected exclusively in the neoplastic epithelium and was found in 6.8% and 46.3% of high-grade prostatic intraepithelial neoplasia (HGPIN) and localized PCa, respectively. In metastatic and locally advanced CRPC, ERG expression was significantly lower, occurring at 36.1% and 37.2%, respectively. In PCa with foamy gland morphology, ERG protein expression was detected in only 18.6% compared with reported rates of about 42%-48% in acinar PCa. Moreover, ERG protein expression and gene rearrangements showed an overall consistency rate of 90.6% (P <.0001). The consistency rate was 100% both in benign glands and HGPIN, and 96.1% in localized PCa. However, it was significantly lower at 76.9% and 85% in node metastatic and CRPC, respectively (P <.0001).

CONCLUSION:

ERG protein expression is restricted to neoplastic prostatic epithelium and is present at lower rates in metastatic and CRPC compared to localized PCa. IHC and FISH concordance rates were significantly lower in node metastatic and CRPC compared to localized PCa, which may suggest different biological and therapeutic implications. The lower rate of ERG protein expression in foamy gland PCa may suggest potential differences for this pattern of PCa at the molecular level.

 

PubMed

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Dr. Nawaid Usmani and team receive funding for their PRIME study!

The PRIME Study – Prevention and Intervention for MEtabolic syndrome:

Androgen deprivation therapy (ADT), and newer manipulations of androgen receptor signaling have improved outcomes for advanced prostate cancer (PCa) patients.  The toxicities of ADT are many, including an increased risk of developing metabolic syndrome (MS; defined as at least 3 of: hyperglycemia; abdominal obesity; hypertriglyceridemia; reduced HDL cholesterol; and/or hypertension). MS is associated with an increased risk of diabetes, cardiovascular disease mortality, stroke mortality, and all-cause mortality.  The prevalence of MS in men receiving ADT is at least 50% and contributes to decreased quality of life and increased non-cancer-related mortality.  Metformin holds promise as a countermeasure to MS development, and also has been shown to suppress PCa growth in pre-clinical models.

We hypothesize that the addition of metformin to ADT will reduce the rates of MS in men with advanced PCa, diminishing important toxicities of a therapy universally used in advanced disease.

We propose a double-blind, randomized phase III study of metformin or placebo in men with PCa starting intermittent ADT. The primary endpoint is the difference in MS rates at 1 year.  Other aims include evaluation of the influence of metformin on: individual MS components at additional time points; mean serum insulin levels and measures of insulin resistance; weight and quality of life.

A finding that metformin reduces MS incidence and/or has other benefits would change practice, as it would provide a practical and inexpensive strategy to reduce toxicity of an intervention employed in most men with advanced PCa.

- Catalina Vasquez