TMPRSS2-ERG Gene Fusion in Prostate Cancer of Central Zone Origin
Michael P Mikulasovich, Melissa L Stanton, Charles C Guo, Michael T Deavers, Ina N Prokhorova, Bogdan A Czerniak, Patricia Troncoso. The University of Texas MD Anderson Cancer Center, Houston, TX
Background: The incidence of prostate cancer originating from the 3 prostate zones varies. Most tumors arise from the peripheral (PZ) and transition (TZ) zones; <5% are considered of central zone (CZ) origin. Previous studies showed that the TMPRSS2-ERG gene fusion status differs substantially between carcinomas of PZ and TZ origin: 30–70% vs. ≤12%. Only limited information is available about the TMPRSS2-ERG gene fusion status in tumors of CZ origin.
Design: We reviewed radical prostatectomy specimens containing foci of possible CZ origin. Only specimens with tumor foci located exclusively within the CZ (identified by its anatomic location and distinct morphologic features) were selected for histologic characterization and TMPRSS2-ERG gene fusion analysis, conducted by using break-apart fluorescence in situ hybridization (FISH) and immunohistochemical analysis (IHC) for ERG protein expression using the ERG antibody (9FY,Biocare Medical, Concord, CA).
Results: We studied a total of 31 specimens with 32 CZ tumor foci (1 specimen had 2 CZ foci). The patients' median age at prostatectomy was 60 years (range, 47–74). The total number of tumor foci in the specimens ranged from 2 to 8 (median, 4). Besides the CZ foci, all specimens had additional tumor foci arising from the PZ + TZ (n = 21), PZ (n = 9), or TZ (n = 1). The CZ tumor foci were nondominant and organ confined in all cases. The CZ tumor foci ranged from <1.0 mm to 10.0 mm with a mean volume of 0.007 cm3 (range, 0.001–0.048 cm3). The mean total tumor volume was 1.099 cm3 (range, 0.030–5.566 cm3). The Gleason score of the CZ tumor foci was 6 in 29 cases, 7 (3+4) in 1 case, and 7 (4+3) in 2 cases. High-grade prostatic intraepithelial neoplasia (HGPIN) in the CZ was identified in 94% of the cases. TMPRSS2-ERG gene fusion was detected in 32% (n = 9) of the 28 cases analyzed by FISH. Of those 9 cases with gene fusion, 5 were caused by gene deletion and 4, by gene translocation. Twenty-two foci analyzed by FISH (8 positive, 14 negative) were also available for ERG protein expression by IHC. The results were concordant in 20 of the 22 (91%) cases.
Conclusions: In this limited study, TMPRSS2-ERG gene fusion was present in 32% and 36% (FISH and IHC results, respectively) of prostate cancers arising from the CZ, with good correlation between the 2 techniques. These results are similar to the incidence range reported for PZ tumors. The association of prostate cancers with HGPIN and the similar incidence of TMPRSS2-ERG gene fusion in PZ and CZ tumors together suggest that similar molecular mechanisms underlie the development of carcinoma in both zones.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 152, Monday Afternoon