TMPRSS2-ERG Gene Fusions in Minimal Prostatic Adenocarcinoma
R Albadine, M Latour, M Haffner, A Toubaji, T Lotan, J Epstein, GJ Netto. Johns Hopkins, Baltimore
Background: Minimal or insignificant prostatic adenocarcinoma (MinPCa) is defined as tumors with insufficient virulence to threaten survival. Given recent suggestion of TMPRSS2-ERG gene fusion association with aggressive PCa phenotype, we aimed to evaluate incidence of TMPRSS2-ERG fusion in MinPCa in comparison with grade matched non-minimal size PCa.
Design: All 33 prostatectomies classified as containing MinPCa (2002-2003) were retrieved. Diagnois of MinPCa (Gleason Score 6 PCa with total tumor volume < 0.5 CC, single section) was confirmed by a urologic pathologist. Tissue microarray (TMA) was constructed from the 33 cases where each tumor and paired benign tissue was represented by up to triplicate,1mm, spots. TMA sections of 59 additional archival PCa were used as controls (26 pT2 non-minimal in size, 31 pT3a and 2 pT3b). FISH analysis was performed using break-apart probes for 5' and 3' regions of ERG. Each spot was scored for presence of TMPRSS2-ERG fusion through deletion or translocation as well as for polyploidy (3 copies) at the ERG locus. At least 50 cells were scored per tumor.
Results: MinPCa: TMPRSS2-ERG fusion was identified in 46% (16/35) of MinPCa. In 87% (14/16) of positive tumors, fusion was due to deletion. The remaining 13% (2/16) of fusions were based on the demonstration of a split in the two juxtaposed probe signals. Ch21 polyploidy fusion and duplication of ERG deletion were not observed in any MinPCa case. Control group: TMPRSS2-ERG fusion was identified in 59% (35/59) of tumors. In 77% (27/35) of positive tumors, fusion was due to deletion. Ch21 polyploidy with fusion was present in 13/59 (22%) while polyploidy with duplicate ERG deletion was found in 6/59 (10%) of control tumors. On statistical analysis, there was no significant difference in TMPRSS2-ERG fusion incidence between the MinPCa and control groups (p=0.2). Statistically significant higher rates of ch 21 polyploidy fusion was present in control group (p=0.0002). A trend approaching statistical significance for higher incidence of ch21 polyploidy with duplicate deletion was also present in the control group (p=0.052).
Conclusions: TMPRSS-ERG fusion rate of 46% is present in MinPCa.The latter is not significantly different from rate of fusion in control group of non-minimal pT2 and pT3 PCa. A higher rate of Ch21 polyploidy is detected in the control group compared to MinPCa. Our finding of a comparable rate of TMPRSS2-ERG fusion in MinPCa and non-minmal PCa argues against its value as a marker of aggressive PCa phenotype.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 1:00 PM
Poster Session II # 104, Monday Afternoon