TMPRSS2-ERG Gene Fusions Are Infrequent in Prostatic Ductal Adenocarcinomas
TL Lotan, A Toubaji, R Albadine, M Latour, M Herawi, AK Meeker, JI Epstein, GJ Netto. Johns Hopkins Hospitals, Baltimore, MD
Background: Ductal adenocarcinoma (DCa) of the prostate is a rare subtype generally associated with a more aggressive clinical course than typical (Gleason pattern 3) acinar adenocarcinoma (ACa). Given its frequent association with an ACa component, some have challenged the concept of prostatic DCa as a distinct variant. We studied the occurrence of TMPRSS2-ERG gene fusions in DCa cases and in their associated ACa component.
Design: Fluorescence in situ hybridization (FISH) using a break apart probe for 5' and 3' ERG was performed on two tissue microarrays (TMA) constructed from 40 radical prostatectomy specimens with DCa. In 20/38 evaluable DCa cases (53%), a concurrent ACa component was scored as well. An additional group of 38 pure ACa cases matched with the DCa group for pathological grade (69% Gleason 7, 31% Gleason 8-10) and stage (39% pT2, 57% pT3) was used as a control. DCa and ACa cases were scored for presence of TMPRSS2-ERG gene fusion through deletion or translocation as well as for polyploidy (3 copies) at the ERG locus. Each case was spotted in quadruplicate and at least 50 cells were scored.
Results: 11% (4/38) of DCa cases had the TMPRSS2-ERG gene fusion, with 75% (3/4) showing the deletion and 25% (1/4) showing the translocation. No cases of duplication of the fusion were observed in the DCa group. In 95% of DCa cases where a concurrent ACa component was available for analysis (19/20), there was concordance for presence/absence of TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of grade and stage-matched pure ACa cases, 45% (17/38) had the gene fusion with 53% (9/17) showing the deletion, 6% (1/17) showing a duplicated deletion, and 41% (7/17) showing the translocation. Compared to the matched ACa cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in DCa (p= 0.002, Fisher's exact test).
Conclusions: The presence of TMPRSS2-ERG gene fusions in some cases of DCa as well as the high concordance of genotype between ductal and acinar components in the same tumor support the concept that prostatic DCa and ACa are closely related histologic variants. However, the significantly lower rate of the gene fusion in DCa cases when compared to grade and stage matched pure ACa cases underscores the fact that enough genetic and potential biologic differences exist between these two histologic subtypes to warrant separate classification for the current time.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 1:00 PM
Poster Session II # 111, Monday Afternoon