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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high tumors.

Original languageEnglish (US)
Pages (from-to)845-853
Number of pages9
JournalProstate
Volume76
Issue number9
DOIs
StatePublished - Jun 15 2016
Externally publishedYes

Fingerprint

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

Keywords

  • BET bromodomain
  • ERG
  • MYC
  • immunohistochemistry (IHC)
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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 M.; Shi, Yang; Hicks, Jessica L.; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M.; Mehra, Rohit.

In: Prostate, Vol. 76, No. 9, 15.06.2016, p. 845-853.

Research output: Contribution to journalArticle

Udager, Aaron M. ; Demarzo, Angelo M. ; 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 ; Vol. 76, No. 9. pp. 845-853.
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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. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high tumors.",
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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 M.

AU - Shi, Yang

AU - Hicks, Jessica L.

AU - Cao, Xuhong

AU - Siddiqui, Javed

AU - Jiang, Hui

AU - Chinnaiyan, Arul M.

AU - Mehra, Rohit

PY - 2016/6/15

Y1 - 2016/6/15

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. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high 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. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high tumors.

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KW - MYC

KW - immunohistochemistry (IHC)

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