Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration-resistant prostate cancer

Aaron M. Udager, Yang Shi, Scott A. Tomlins, Ajjai Alva, Javed Siddiqui, Xuhong Cao, Kenneth J. Pienta, Hui Jiang, Arul M. Chinnaiyan, Rohit Mehra

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND. ERG 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 ERG 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). METHODS. 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 ERG 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). RESULTS. All 16 (100%) ERG rearrangement negative (ERGneg) patients were also negative for ERG tumor cell expression (i.e., IHC product score = 0). Of the 10 ERG rearrangement positive (ERG pos) 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 ERGpos patients, five (63%) had at least one tumor site without any detectable ERG expression. For a given ERGpos 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. CONCLUSIONS. These data reveal frequent discordance between ERG IHC and ERG FISH in ERGpos patients from this unique cohort of heavily treated lethal mCRPC.

Original languageEnglish (US)
Pages (from-to)1199-1208
Number of pages10
JournalProstate
Volume74
Issue number12
DOIs
StatePublished - Sep 2014
Externally publishedYes

Fingerprint

Gene Rearrangement
Castration
Autopsy
Prostatic Neoplasms
Immunohistochemistry
Androgen Receptors
Prostate-Specific Antigen
Neoplasms
Proteins
Fluorescence In Situ Hybridization
Antigen Receptors
Staining and Labeling
Sensitivity and Specificity

Keywords

  • TMPRSS2-ERG
  • androgen receptor (AR)
  • fluorescent in situ hybridization (FISH)
  • immunohistochemistry (IHC)
  • rapid autopsy

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration-resistant prostate cancer. / Udager, Aaron M.; Shi, Yang; Tomlins, Scott A.; Alva, Ajjai; Siddiqui, Javed; Cao, Xuhong; Pienta, Kenneth J.; Jiang, Hui; Chinnaiyan, Arul M.; Mehra, Rohit.

In: Prostate, Vol. 74, No. 12, 09.2014, p. 1199-1208.

Research output: Contribution to journalArticle

Udager, Aaron M. ; Shi, Yang ; Tomlins, Scott A. ; Alva, Ajjai ; Siddiqui, Javed ; Cao, Xuhong ; Pienta, Kenneth J. ; Jiang, Hui ; Chinnaiyan, Arul M. ; Mehra, Rohit. / Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration-resistant prostate cancer. In: Prostate. 2014 ; Vol. 74, No. 12. pp. 1199-1208.
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title = "Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration-resistant prostate cancer",
abstract = "BACKGROUND. ERG 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 ERG 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). METHODS. 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 ERG 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). RESULTS. All 16 (100{\%}) ERG rearrangement negative (ERGneg) patients were also negative for ERG tumor cell expression (i.e., IHC product score = 0). Of the 10 ERG rearrangement positive (ERG pos) 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 ERGpos patients, five (63{\%}) had at least one tumor site without any detectable ERG expression. For a given ERGpos 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. CONCLUSIONS. These data reveal frequent discordance between ERG IHC and ERG FISH in ERGpos patients from this unique cohort of heavily treated lethal mCRPC.",
keywords = "TMPRSS2-ERG, androgen receptor (AR), fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), rapid autopsy",
author = "Udager, {Aaron M.} and Yang Shi and Tomlins, {Scott A.} and Ajjai Alva and Javed Siddiqui and Xuhong Cao and Pienta, {Kenneth J.} and Hui Jiang and Chinnaiyan, {Arul M.} and Rohit Mehra",
year = "2014",
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TY - JOUR

T1 - Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration-resistant prostate cancer

AU - Udager, Aaron M.

AU - Shi, Yang

AU - Tomlins, Scott A.

AU - Alva, Ajjai

AU - Siddiqui, Javed

AU - Cao, Xuhong

AU - Pienta, Kenneth J.

AU - Jiang, Hui

AU - Chinnaiyan, Arul M.

AU - Mehra, Rohit

PY - 2014/9

Y1 - 2014/9

N2 - BACKGROUND. ERG 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 ERG 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). METHODS. 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 ERG 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). RESULTS. All 16 (100%) ERG rearrangement negative (ERGneg) patients were also negative for ERG tumor cell expression (i.e., IHC product score = 0). Of the 10 ERG rearrangement positive (ERG pos) 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 ERGpos patients, five (63%) had at least one tumor site without any detectable ERG expression. For a given ERGpos 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. CONCLUSIONS. These data reveal frequent discordance between ERG IHC and ERG FISH in ERGpos patients from this unique cohort of heavily treated lethal mCRPC.

AB - BACKGROUND. ERG 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 ERG 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). METHODS. 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 ERG 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). RESULTS. All 16 (100%) ERG rearrangement negative (ERGneg) patients were also negative for ERG tumor cell expression (i.e., IHC product score = 0). Of the 10 ERG rearrangement positive (ERG pos) 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 ERGpos patients, five (63%) had at least one tumor site without any detectable ERG expression. For a given ERGpos 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. CONCLUSIONS. These data reveal frequent discordance between ERG IHC and ERG FISH in ERGpos patients from this unique cohort of heavily treated lethal mCRPC.

KW - TMPRSS2-ERG

KW - androgen receptor (AR)

KW - fluorescent in situ hybridization (FISH)

KW - immunohistochemistry (IHC)

KW - rapid autopsy

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U2 - 10.1002/pros.22836

DO - 10.1002/pros.22836

M3 - Article

C2 - 25043157

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VL - 74

SP - 1199

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JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 12

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