title: Expression of ERG protein in prostate cancer: variability and biological correlates.
abstract: Prostate cancer is the second leading cause of cancer-related death of men in the USA. The TMPRSS2/ERG (T/E) fusion gene is present in approximately 50% of prostate cancers and promotes tumor progression in vivo. The presence of the T/E fusion gene is strongly associated with the expression of ERG protein, but emerging evidence indicates a significant interfocal and intrafocal variability in the levels of ERG protein expression. We therefore analyzed ERG protein expression by image analysis to objectively quantitate the extent of such heterogeneity, and confirmed significant interfocal and intrafocal variability of ERG protein expression levels in cancer expressing ERG. To define the pathways associated with ERG and its variable expression in prostate cancer, we have analyzed the correlations of ERG expression, as evaluated by immunohistochemistry, with 46 key proteins associated with signal transduction, transcriptional control, and other processes using a large tissue microarray with more than 500 prostate cancers. We found a significant correlation of ERG expression with the markers of activation of the PI3K, MYC, and NFκB pathways, which had previously been linked directly or indirectly to ERG expression. We have also identified significant correlations with novel proteins that have not been previously linked to ERG expression, including serum response factor, the p160 coactivator SRC1, and Sprouty1. Notably, SKP2 only correlated with a high level of ERG protein expression. Thus ERG expression is variable in prostate cancer and is associated with activation of multiple pathways and proteins including several potentially targetable pathways.
authors.affiliation: Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ayala
authors.affiliation: Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Frolov
authors.affiliation: Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA.
authors.forename: Deyali
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA.
authors.forename: Dandan
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Hilsenbeck
authors.affiliation: Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA Department of Pathology and Laboratory MedicineUniversity of Texas Health Sciences Center Medical School, Houston, Texas, USADan L. Duncan Cancer CenterHouston, Texas, USADepartment of Pathology and ImmunologyBaylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USADepartment of Veterans AffairsMichael E. DeBakey VA Medical Center, Houston, Texas 77030, USA mittmann@bcm.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Ittmann
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
keywords: MYC; NFκB; PTEN; TMPRSS2/ERG; prostate cancer