Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration‐resistant prostate cancer. Issue 12 (7th July 2014)

• Record Type: Journal Article
• Authors: Udager, Aaron M.; Shi, Yang; Tomlins, Scott A.; Alva, Ajjai; Siddiqui, Javed; Cao, Xuhong; Pienta, Kenneth J.; Jiang, Hui; Chinnaiyan, Arul M.; Mehra, Rohit
• Is Part Of: Prostate. Volume 74:Issue 12(2014)
• Page Start: 1199
• Page End: 1208
• Publication Date: 2014-07-07
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22836
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22836-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p> <italic>ERG</italic> rearrangements in localized prostate cancer can be detected with high sensitivity and specificity by immunohistochemistry (IHC). However, recent data suggest that ERG IHC may be less sensitive for <italic>ERG</italic> rearrangements in castration‐resistant prostate cancer (CRPC). Thus, we sought to examine ERG protein expression in a cohort of rapid autopsy patients with lethal metastatic CRPC (mCRPC).</p> </sec> <sec id="pros22836-sec-0002" sec-type="section"> <title>METHODS</title> <p>A tissue microarray (TMA) of tumor sites from these patients was evaluated for ERG, prostate‐specific antigen (PSA), and androgen receptor (AR) expression by IHC and correlated with <italic>ERG</italic> rearrangement status by fluorescent in situ hybridization (FISH). IHC was scored as the product of tumor cell staining intensity (0–3) and percentage of cells positive (0–100) (overall product score range = 0–300).</p> </sec> <sec id="pros22836-sec-0003" sec-type="section"> <title>RESULTS</title> <p>All 16 (100%) <italic>ERG</italic> rearrangement negative (<italic>ERG</italic><sup>neg</sup>) patients were also negative for ERG tumor cell expression (i.e., IHC product score = 0). Of the 10 <italic>ERG</italic> rearrangement positive (<italic>ERG</italic><sup>pos</sup>) patients, two (20%) were completely negative for ERG tumor cell expression, while eight (80%) had weak ERG expression (median IHC product score = 5–110). Of these eight <italic>ERG</italic><sup>pos</sup> patients, five (63%) had at least one tumor site without any detectable ERG expression. For a given <italic>ERG</italic><sup>pos</sup> patient, ERG expression varied both between and within tumor sites; AR and PSA expression also varied between tumor sites, and there was no significant correlation between ERG and AR or PSA expression.</p> </sec> <sec id="pros22836-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>These data reveal frequent discordance between ERG IHC and <italic>ERG</italic> FISH in <italic>ERG</italic><sup>pos</sup> patients from this unique cohort of heavily treated lethal mCRPC. <italic>Prostate 74:1199–1208, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>