Chromosome 21 Copy Number but Not TMPRSS2-ERG Fusion Predicts Outcome in Prostatic Adenocacrcinoma: A Large Case-Control Radical Prostatectomy Cohort Analysis
A Toubaji, R Albadine, A Meeker, H Fedor, A DeMarzo, JI Epstein, E Platz, GJ Netto. Johns Hopkins, Baltimore
Background: TMPRSS2-ERG gene fusion has been reported to be present in up to 70% of all PCa with hereto conflicting findings in relation to its clinical significance. In the current study, we aimed to evaluate the role of TMPRSS2-ERG fusion in predicting disease progression using FISH analysis applied to a well characterized set of PCa case-control cohort.
Design: 9 TMAs containing paired tumor and normal tissues of 158 cases and 158 control radical prostatectomies matched for grade, stage, ethnicity and ptage. All RRPs were performed in our institution between1993-2000. Progression was defined as development of biochemical recurrence, clinical evidence of metastasis or death of PCa. FISH analysis was performed using break-apart probes for the 5' and 3' regions of ERG. Each spot was scored for presence of TMPRSS2-ERG gene fusion through deletion or split as well as for polyploidy (3 copies) at the ERG locus. At least 50 cells were scored per spot.
Results: Findings are summarized in table 1.
|Fusion||Deletion||Split||Duplicated Deletion||Polyploidy + Deletion||Polyploidy +Split||ch21 Polyploidy without fusion|
Presence of fusion due to either a deletion or split event was not associated with progression. Likewise, neither the presence of duplicated ERG deletion, duplictated split, presence of ch21 polyploidy with single allele ERG deletion nor the presence of ch21 polyploidy with single allele ERG split were associated with progression. ERG gene polyploidy without fusion was significantly associated with progression in our cohort (Hazard ratio 2.05; 95% CI: 1.2-3.5, p=0.01).
Conclusions: We found no correlation between presence of TMPRSS2-ERG fusion (or type of fusion) and progression in our large well characterized case-control cohort. Progression was significantly associated with presence of ch21 polyploidy without fusion.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:00 AM
Platform Session: Section A, Monday Morning