Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer

Potential opportunities for synergistic targeted therapeutics

Aaron M. Udager, Angelo Michael Demarzo, Yang Shi, Jessica L. Hicks, Xuhong Cao, Javed Siddiqui, Hui Jiang, Arul M. Chinnaiyan, Rohit Mehra

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. METHODS: Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range=0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. RESULTS: 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb=0.149, P=0.045), although this correlation was strongest in secondary nodules (rpb=0.520, P=0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. CONCLUSIONS: Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors.

Original languageEnglish (US)
JournalProstate
DOIs
StateAccepted/In press - 2016

Fingerprint

Prostatic Neoplasms
Neoplasms
Proteins
Prostatectomy
Transcription Factors
Therapeutics
Immunohistochemistry
Recurrence
Gene Fusion
Paraffin
Formaldehyde
Staining and Labeling

Keywords

  • BET bromodomain
  • ERG
  • Immunohistochemistry (IHC)
  • MYC
  • Prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer : Potential opportunities for synergistic targeted therapeutics. / Udager, Aaron M.; Demarzo, Angelo Michael; Shi, Yang; Hicks, Jessica L.; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M.; Mehra, Rohit.

In: Prostate, 2016.

Research output: Contribution to journalArticle

Udager, Aaron M. ; Demarzo, Angelo Michael ; Shi, Yang ; Hicks, Jessica L. ; Cao, Xuhong ; Siddiqui, Javed ; Jiang, Hui ; Chinnaiyan, Arul M. ; Mehra, Rohit. / Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer : Potential opportunities for synergistic targeted therapeutics. In: Prostate. 2016.
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title = "Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics",
abstract = "BACKGROUND: Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. METHODS: Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range=0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. RESULTS: 29.1{\%} of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0{\%} of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb=0.149, P=0.045), although this correlation was strongest in secondary nodules (rpb=0.520, P=0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. CONCLUSIONS: Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors.",
keywords = "BET bromodomain, ERG, Immunohistochemistry (IHC), MYC, Prostate cancer",
author = "Udager, {Aaron M.} and Demarzo, {Angelo Michael} and Yang Shi and Hicks, {Jessica L.} and Xuhong Cao and Javed Siddiqui and Hui Jiang and Chinnaiyan, {Arul M.} and Rohit Mehra",
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journal = "Prostate",
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TY - JOUR

T1 - Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer

T2 - Potential opportunities for synergistic targeted therapeutics

AU - Udager, Aaron M.

AU - Demarzo, Angelo Michael

AU - Shi, Yang

AU - Hicks, Jessica L.

AU - Cao, Xuhong

AU - Siddiqui, Javed

AU - Jiang, Hui

AU - Chinnaiyan, Arul M.

AU - Mehra, Rohit

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. METHODS: Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range=0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. RESULTS: 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb=0.149, P=0.045), although this correlation was strongest in secondary nodules (rpb=0.520, P=0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. CONCLUSIONS: Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors.

AB - BACKGROUND: Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. METHODS: Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range=0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. RESULTS: 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb=0.149, P=0.045), although this correlation was strongest in secondary nodules (rpb=0.520, P=0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. CONCLUSIONS: Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors.

KW - BET bromodomain

KW - ERG

KW - Immunohistochemistry (IHC)

KW - MYC

KW - Prostate cancer

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U2 - 10.1002/pros.23175

DO - 10.1002/pros.23175

M3 - Article

JO - Prostate

JF - Prostate

SN - 0270-4137

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