ERG Rearrangement Is Associated with an Earlier Age at Diagnosis in a PSA-Screening Clinical Trial Cohort from Tyrol (Austria)
Francesca Demichelis, Georg Schaefer, Kyung Park, Birgit Stenzel, Juan Miguel Mosquera, Sunita Setlur, Charles Lee, Helmut Klocker, Mark Rubin. Weill Medical College of Cornell University, New York, NY; Centre for Integrative Biology, University of Trento, Trento, Italy; Innsbruck Medical University, Innsbruck, Austria; Brigham and Women's Hospital and Harvard Medical School, Boston, MA
Background: The Tyrol Prostate Specific Antigen (PSA) Screening Cohort, a population-based cohort of men tested with PSA for early detection and treatment of prostate cancer (PCa), started in 1993 and includes men aged 45 to 75. PSA serum levels measurements were used to detect men at risk for PCa. Urological examination and prostate biopsy (PB) was recommended with age-adjusted serum PSA level thresholds. About one third of the PCa cases were detected in men with PSA 2.0 to 4.0 ng/ml. Information on digital rectal examination (DRE), ultrasonography (US), transrectal ultrasound-guided PB, and radical prostatectomy (RP) specimens was also available. We investigated the prevalence of ERG rearrangement in cases of this PSA-screening clinical trial cohort, and sought to describe associations with Gleason score, tumor stage, and age at diagnosis, and to investigate a previously reported association between gene rearrangement and a SNP in TMPRSS2.
Design: Archived RP specimens (n=399) and corresponding blood samples were obtained. ERG IHC was performed on RP slides using Ventana Discovery XT platform. Semiquantitative ERG expression was evaluated, with moderate (2+) and strong (3+) intensities considered as positive. Genotype data was determined by Affymetrix Human SNP Array 6.0 with DNA extracted from peripheral blood mononuclear cells. rs915823 was identified as tag SNP for the previously reported rs12329760 using HapMap genotypes (R2 > 0.8).
Results: ERG rearrangement for 399 men from Tyrol cohort was 60.4%. ERG fusion status was associated with earlier age at diagnosis (p=0.003), but not with tumor grade or stage. The risk SNP (rs915823) was queried in 351 out of 399 subjects with known ERG fusion status. There was no overall association between the SNP alleles and ERG fusion. However, we observed an association between the C allele of the SNP and higher levels of pre-operative PSA (p=0.02).
Conclusions: ERG rearrangement PCa prevalence in the Tyrol cohort is higher than generally reported in other Caucasian (∼50%), Japanese (∼16%) and African American (∼30%) cohorts. We did not detect association between the TMPRSS2 SNP and ERG rearrangement. However, the C allele was associated with higher levels of pre-operative PSA. ERG fusion status was strongly associated with earlier age at diagnosis of PCa, even after controlling for PSA levels.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:30 PM
Platform Session: Section A, Tuesday Afternoon