[741] TMPRSS2-ERG Gene Fusion in Small Cell Carcinoma of the Prostate

JY Dancer, G Zuo, C Soto, P Troncoso, BA Czerniak, CC Guo. University of Texas MD Anderson Cancer Center, Houston, TX

Background: The TMPRSS2-ERG gene fusion has been frequently found in prostatic adenocarcinoma. Small cell carcinoma of the prostate is a highly aggressive disease with distinct pathologic and clinical features that are significantly different from those of conventional prostatic adenocarcinoma. In this study, we examined the TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate.
Design: We searched our pathology files from 1986 to 2008 and identified 14 patients with small cell carcinoma of the prostate. The specimens from the patients included prostate biopsy specimens (n=4), radical prostatectomies (n=5), and biopsy specimens of metastatic sites (n=2). The TMPRSS2-ERG gene fusion was evaluated by fluorescence in situ hybridization (FISH) using the ERG gene break-apart probe. Four cases of small cell carcinoma of the urinary bladder were also included for comparison.
Results: The average age of the 14 patients was 68.9 years (range, 44.0-85.0 years). Eleven patients had a previous diagnosis of prostate adenocarcinoma. In 13 cases, focal high-grade prostatic adenocarcinoma was also present in the specimens. In 1 case, no adenocarcinoma was present. In 12 cases, neuroendocrine differentiation of small cell carcinoma was confirmed by positive immunohistochemical staining for synaptophysin, chromogranin, and CD 56. Rearrangements in the ERG gene were present in eight cases (57%) of small cell carcinoma of the prostate. In all 8 cases, the rearrangement was associated with a deletion of the 5' end of the ERG gene. The rearrangement in the ERG gene was not present in any of the 4 cases of small cell carcinoma of the bladder. Clinical follow-up was available for 12 patients. The patients had received hormonal therapy (n=12), chemotherapy (n=12), radiation therapy (n=11), and radical prostatectomy (n=5). Eleven patients developed distant metastasis. Ten patients died at a mean of 64.8 months after diagnosis (range, 5.0-168.0 months). Two patients were alive with the disease at 55 and 58 months after diagnosis, respectively.
Conclusions: The rearrangement in the ERG gene was frequently present in small cell carcinomas of the prostate. The high prevalence of the TMPRSS2-ERG gene fusion in small cell carcinoma as well as conventional adenocarcinoma implies that small cell carcinoma may evolve from conventional adenocarcinoma in the prostate. Our finding also suggests that the TMPRSS2-ERG gene fusion may be helpful in distinguishing small cell carcinoma of prostatic origin from those of other origins.
Category: Genitourinary (including renal tumors)

Monday, March 9, 2009 1:00 PM

Poster Session II # 105, Monday Afternoon