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ERG-TMPRSS2 rearrangement is shared by concurrent prostatic adenocarcinoma and prostatic small cell carcinoma and absent in small cell carcinoma of the urinary bladder: evidence supporting monoclonal origin

2011-08-02 16:02:09

Modern Pathology; 2013 Aug; 24(8):1120-7


Sean R Williamson, Shaobo Zhang, Jorge L Yao, Jiaoti Huang, Antonio Lopez-Beltran, Steven Shen, Adeboye O Osunkoya, Gregory T MacLennan, Rodolfo Montironi, and Liang Cheng



Introduction



Prostatic carcinoma is a heterogeneous disease process with a wide spectrum of light microscopic morphologic features, biological behavior, and frequent multifocality. In particular, small cell carcinoma of the prostate is a rare and aggressive variant, comprising ~0.5–2.0% of prostatic carcinoma, that exhibits unique clinicopathological characteristics, including frequent metastasis to visceral and other sites uncommon for prostate cancer, such as liver, lung, and brain. Patients typically are found to have lower levels of serum prostate-specific antigen and a poorer response to androgen deprivation therapy. Because of its rarity and unusual behavior, several differential diagnostic dilemmas may accompany the diagnosis of small cell carcinoma of the prostate, particularly identification of a small cell carcinoma tumor originating from an unknown primary site10 and distinguishing prostatic primary tumors from those of the urinary bladder. Recent studies have identified gene fusions between members of the ETS family of genes and transmembrane protease, serine 2 (TMPRSS2) to be a significant event in prostate cancer; in particular, fusion of transcriptional regulator ETS-related gene (ERG) and TMPRSS2. Interestingly, these fusions appear to represent a specific early event in prostatic carcinogenesis seen in many of the variant histological forms of prostatic carcinoma but absent in epithelial neoplasms of other organs. Therefore, molecular testing for ERG–TMPRSS2 rearrangement may be helpful for not only resolving the organ of origin in an individual case, but also more globally, elucidating the histogenesis of prostatic small cell carcinoma.



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