Increased androgen receptor gene copy number is associated with TMPRSS2‐ERG rearrangement in prostatic small cell carcinoma. Issue 9 (29th April 2014)

• Record Type: Journal Article
• Authors: Wang, Lisha; Williamson, Sean R.; Zhang, Shaobo; Huang, Jiaoti; Montironi, Rodolfo; Davison, Darrell D.; Wang, Mingsheng; Yao, Jorge L.; Lopez‐Beltran, Antonio; Osunkoya, Adeboye O.; MacLennan, Gregory T.; Baldridge, Lee Ann; Du, Xiang; Cheng, Liang
• Is Part Of: Molecular carcinogenesis. Volume 54:Issue 9(2015:Sep.)
• Page Start: 900
• Page End: 907
• Publication Date: 2014-04-29
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22162
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mc22162-sec-0001" sec-type="section"> <p>Small cell carcinoma of the prostate (PSCC) is a highly aggressive malignancy that often develops in patients previously treated with hormonal therapy for metastatic prostatic acinar adenocarcinoma. The <italic>TMPRSS2‐ERG</italic> gene rearrangement is highly specific for prostate cancer and shared by PSCC; however, the role of androgen receptor (<italic>AR</italic>) gene alterations and interaction with <italic>TMPRSS2‐ERG</italic> rearrangement are incompletely understood in PSCC. Sixty‐one cases of PSCC were examined for <italic>AR</italic> gene copy number and <italic>TMPRSS2‐ERG</italic> rearrangement by fluorescence in situ hybridization (FISH) and AR protein expression by immunohistochemistry. Of 61 cases of PSCC, 51% (31/61) demonstrated increased <italic>AR</italic> gene copy number (FISH+), 54% (33/61) were positive for <italic>TMPRSS2‐ERG</italic> gene fusion, and 38% (23/61) showed AR protein expression. Of the 31 <italic>AR</italic> FISH+ cases, 23 also showed <italic>TMPRSS2‐ERG</italic> gene fusion, and 16 expressed AR protein. Of the 33 cases with <italic>TMPRSS2‐ERG</italic> fusion, 28 were <italic>AR</italic> FISH+ or expressed AR protein. Statistically significant correlations were observed between <italic>AR</italic> gene copy number or AR protein expression and <italic>TMPRSS2‐ERG</italic> gene fusion (<italic>P</italic> = 0.001 and <italic>P</italic> = 0.03, respectively). In summary, high <italic>AR</italic> gene copy number emerges during the development of PSCC, often in association with <italic>TMPRSS2‐ERG</italic> rearrangement. This potential mechanism warrants further study. Improvement will come from understanding the biology of the disease and integrating new therapies into the treatment of this rare and aggressive tumor. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>