Differential Gene Expression In Normal Prostate Epithelium Of Men With/without Prostate Cancer: Evidence For A Prostate Cancer Field Effect

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology;  Genetics
Article Date: 19 Jun 2008 - 3:00 PDT

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ORLANDO, FL (UroToday.com) - Several solid tumors are associated with molecular changes in adjacent, histologically normal cells, the so-called "field effect". This field effect may predispose the normal cells to the development of frank malignancy. These investigators sought to determine if normal epithelium from prostates harboring prostatic adenocarcinoma harbor changes in gene expression suggestive of pre-malignancy or filed effect.

Prostate needle biopsies from 15 men with high grade (Gleason 8-10) prostate cancer and 15 age- and BMI-matched controls were identified from a pool of biopsies collected from >500 men since 2003. Normal epithelia from each patient were isolated via laser capture microdissection (LCM) of fresh frozen bipsy tissue. Biopsies were reviewed by a pathologist prior to LCM to ensure only normal epithelia was captured. RNA was isolated from each sample, amplified, then utilized for microarray analysis using the Agilent Human 4X4X4 array platform. The data were analyzed by paired two-sample T-test using Significance Analysis of Microarrays (SAM). Quantitative PCR (qPCR) was also used to determine the expression of various genes of interest identified by microarray analysis.

One control patient had Gleason 7 prostate cancer on repeat biopsy during the data analysis period and thus was excluded. The remaining 14 control and 15 cancer samples were included in the final analysis. Microarray analysis revealed that these 2 groups had very similar patterns of gene expression overall. SAM analysis found significant q values (q<1%) in 2 genes previously associated with prostate cancer, namely FOLH1/PSMA and SSTR1. The researchers examined other prostate cancer-associated genes by qPCR and found significant differential expression changes in ERG, HOXC4, HOXC5 and MME, although other cancer markers (HPN, AMACR, FASN, SPOCK1, MYO6, TPD52, EZH2) were not different between the 2 groups. Interestingly, the elevated ERG expression in the normal epithelia adjacent to prostate cancer did not appear to be associated with the TMPRSS2:ERG fusion with the exception of one patient.

They conclude that overall gene expression profiles between normal prostatic epithelia of patients with and without prostate cancer are very similar. However, several of the differentially expressed genes found in this study have been implicated in prostate cancer progression and prognosis in prior studies, and thus may represent the earliest events in prostate carcinogenesis.

Presented by Michael C Risk, MD, Ilsa Coleman, MD, Ruthy Dumpit, MD, Robert C Gentleman, MD, Alan R Kristal, MD, Beatrice S Knudsen, MD, Peter S Nelson, MD, Daniel W Lin, MD, at the Annual Meeting of the American Urological

Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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