ERG Rearrangement Is Present in a Subset of Transition Zone Prostatic Tumors
SM Falzarano, M Navas, K Simmerman, MA Rubin, EA Klein, M Zhou, C Magi-Galluzzi. Cleveland Clinic, Cleveland, OH; Summa Health System, Akron, OH; Cornell University, New York, NY; University of Siena, Siena, Italy
Background: Most prostate cancers (PCA) exhibit a unique chromosomal aberration in chromosome 21. In approximately 90% of cases, the rearrangement is characterized by the fusion of the protein TMPRSS2 with the oncogene ERG. A recent study has shown that the TMPRSS2-ERG gene fusion is lacking in PCA arising from the transition zone (TZ) of the prostate.
Design: A tissue microarray of TZ-predominant PCA from 62 patients who underwent radical prostatectomies (RP) between 2004 and 2009 was constructed. Two separate tumor nodules, one in the TZ (n=62) and, when available, one in the peripheral zone (PZ) (n=35) were selected for gene fusion analysis. TMPRSS2-ERG fusion status was determined using a multicolor interphase fluorescence in situ hybridization assay for ERG break-apart. A nucleus with an ERG break-apart (indicative of a TMPRSS2-ERG fusion) shows split apart of one juxtaposed red-green signal pair resulting in a single red and green signal. The telomeric green signal may be lost due to deletion resulting in one yellow and one red signal in a nucleus with rearrangement through deletion.
Results: The patients median age was 59 years (range 42-81). PCA Gleason score (GS) was 6 (34%), 7 (55%); 7 with pattern 5 (5%) and 9 (6%). The mean tumor volume was 294 mm2 (>2.0cc). Fifty-nine/62 cases were informative. TMPRSS2-ERG gene fusion was present in 11.9% (7/59) of TZ tumors, and in 34.3% (12/35) of PZ tumors. Gene fusion through deletion occurred in 4/7 TZ (57.1%) and 6/12 PZ (50%) cases. In three patients, the TMPRSS2-ERG gene fusion was present in both TZ and PZ tumors: in one case the rearrangement was associated with a deletion in both tumors; in the other two cases, a deletion was present either in the TZ or in the PZ tumor.
Conclusions: PCA arising from TZ is biologically and genetically different from PZ tumors. Although ERG rearrangement is prevalent in PZ tumors, is present also in a subset of TZ prostate cancer (11.9%). The lower frequency of gene fusion in TZ PCA may suggest a different carcinogenic pathway. Further studies are needed to address whether such chromosomal aberration difference may account for the clinical and biological differences between TZ and PZ tumors.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 129, Wednesday Afternoon