title: Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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. Prostate 76:845-853, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Udager
authors.affiliation: Department of Pathology, The Sidney Kimmel Comprehensive Cancer Center and The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: DeMarzo
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan.|Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathology, The Sidney Kimmel Comprehensive Cancer Center and The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hicks
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, Michigan.
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.|Michigan Center for Translational Pathology, Ann Arbor, Michigan.|Department of Urology, University of Michigan Health System, Ann Arbor, Michigan.|Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan.|Howard Hughes Medical Institute, Ann Arbor, Michigan.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan.|Michigan Center for Translational Pathology, Ann Arbor, Michigan.|Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050596:Oncogene Fusion; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D000071230:Transcriptional Regulator ERG / Q000235:genetics / Q000378:metabolism
chemical_list: C072312:ERG protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D000071230:Transcriptional Regulator ERG
keywords: BET bromodomain; ERG; MYC; immunohistochemistry (IHC); prostate cancer