UroToday - A genetic rearrangement with fusion of the TMPRSS2 prostate-specific gene with the ERG transcription factor is commonly found in prostate cancer (CaP) and has oncogenic potential. How frequently it occurs varies in the literature. In the July issue of Clinical Cancer Research, Dr. Juan-Miguel Mosquera and colleagues investigated the incidence of TMPRSS2-ERG fusion status in 140 prostate biopsy specimens using fluorescent in situ hybridization.

The cohort patients were part of an Early Detection Research Network study from five separate urological practices in Massachusetts and Michigan. Prostate cancer was histologically confirmed in 100 men and 34 control benign samples (6 samples were non-assessable by FISH). TMPRSS2-ERG fusion status was evaluated in at least 50 nuclei from each sample. Cross-evaluation among pathologists revealed complete agreement on the TMPRSS2-ERG fusion status.

Among the 100 CaP specimens, 46 were found to have the TMPRSS2-ERG gene fusion. From these positive gene fusion cases, 63% showed fusion through deletion and 37% showed fusion through insertion. None of the 34 benign samples showed fusion, and this included 9 benign biopsies from patients with CaP. The investigators also noted that normal prostatic glands adjacent to CaP areas in the same biopsy were negative for the TMPRSS2-ERG gene fusion. Pathological features associated with TMPRSS2-ERG fusion included cribriform growth pattern, blue-tinged mucin, and macro-nucleoli in addition to lower PSA density. Gleason score was not associated with TMPRSS2-ERG gene fusion. Four cases of TMPRSS2-ERG gene fusion were found in cases of high-grade PIN.

The TMPRSS2-ERG gene fusion is associated with worse prognosis with higher tumor stage and tumor-specific death or metastasis. This study supports data that the TMPRSS2-ERG gene fusion occurs in almost half of patients diagnosed with CaP.

Mosquera JM, Mehra R, Regan MM, Perner S, Genega EM, Bueti G, Shah RB, Gaston S, Tomlins SA, Wei JT, Kearney MC, Johnson LA, Tang JM, Chinnaiyan AM, Rubin MA, Sanda MG
Clin Cancer Res. 2009 Jul 15;15(14):4706-11.
doi:10.1158/1078-0432.CCR-08-2927

UroToday Contributing Editor Christopher P. Evans, MD, FACS

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