ERG Gene Rearrangement Is Common in Prostatic Small Cell Carcinomas
TL Lotan, W Wang, NS Gupta, A Toubaji, MC Haffner, AK Meeker, JI Epstein, GJ Netto. Johns Hopkins Hospitals, Baltimore, MD; Henry Ford Hospital, Detroit, MI
Background: Small cell carcinoma (SCC) of the prostate is a rare subtype with an aggressive clinical course which often occurs with an associated acinar prostatic adenocarcinoma (ACa) component. Despite the frequent occurrence of TMPRSS2-ERG gene rearrangements in ACa, the incidence of these rearrangements in prostatic SCC is unclear. We examined the occurrence of ERG gene rearrangements in proven prostatic SCC cases and their associated ACa component.
Design: FISH using a break-apart probe for 5' and 3' ERG was performed on a TMA constructed from 29 cases of prostatic SCC received in consultation. Of 22 evaluable cases, 15 (68%) were transurethral resections of the prostate (TURP), 4 (18%) were bladder biopsies, 2 (9%) were prostate needle biopsies and 1 (4%) was a radical prostatectomy. The average patient age was 73 years. In 82% (18/22) of evaluable cases, a concurrent or prior history of prostatic ACa was established, while 9% (2/22) of cases were diagnosed by positive PSA immunostaining and 9% (2/22) of cases had a documented negative cystoscopy. 27% (6/22) of cases had a concurrent ACa component present on the TMA for analysis. Cases were scored for presence of ERG gene rearrangement through deletion or translocation at the ERG locus. Each case was spotted in quadruplicate and at least 50 cells were scored.
Results: 45% (10/22) of prostatic SCC cases had ERG gene rearrangements, with 80% (8/10) showing the deletion and 20% (2/10) showing the translocation. In 83% (5/6) of SCC cases where a concurrent conventional prostatic ACa component was available for analysis, there was concordance for presence/absence of ERG gene rearrangement between the different histologic subtypes. 50% (3/6) of cases showed concurrent ERG deletion in both subtypes, and 17% (1/6) of cases showed an ERG translocation in the SCC component and an ERG deletion in the ACa component. 33% (2/6) showed no ERG rearrangement in either component.
Conclusions: The presence of ERG gene rearrangements in nearly half of prostatic SCC cases is a similar rate of rearrangement to that found in prostatic ACa. Further, the high concordance rate of ERG rearrangement between the SCC and ACa components in a given patient supports a common origin for these two subtypes of prostate cancer. Finally, as ERG rearrangements have not been documented to date in non-prostatic neoplasms, the presence of ERG rearrangement in a small cell carcinoma of unknown primary is highly suggestive of prostatic origin.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 1:00 PM
Poster Session II # 110, Monday Afternoon