title: A comparative study of ERG status assessment on DNA, mRNA, and protein levels using unique samples from a Swedish biopsy cohort.
abstract: The ERG rearrangement is identified in approximately 50% of prostate cancer screened cohorts and is known to be highly specific. This genetic aberration, most commonly leading to the TMPRSS2-ERG fusion, but also SLC45A3-ERG or NDRG1-ERG fusions, all leading to an overexpression of a truncated ERG protein. Most studies have applied in situ hybridization (FISH) methods or mRNA-based assays to investigate the ERG status. Recently, studies showed that ERG protein levels assessed by ERG antibodies can be used as a surrogate marker for ERG rearrangement. In the current study, we investigate ERG status on a series of diagnostic biopsies using DNA-based, mRNA-based, and protein-based assays. We formally compared 3 assay results (ie, FISH, fusion mRNA, and immunohistochemistry) to identify which method could be most appropriate to use when having limited amount of tissue. ERG rearrangement was found in 56% of the cases. Comparing ERG rearrangement status by FISH with ERG overexpression and TMPRSS2-ERG fusion transcript we found 95.1% (154/162, Fisher exact test 9.50E-36) and 85.2% (138/162, Fisher exact test 7.26E-22) concordance, respectively. We show that the ERG antibody highly correlates with the ERG rearrangement with high sensitivity and specificity. We also identified the most common TMPRSS2-ERG isoform in the majority of ERG rearranged cases. These results provide compelling evidence that the ERG antibody can be used to further investigate the role of ERG in prostate cancer.
authors: Departments of *Laboratory Medicine †Urology ‡Institute of Health and Medical Science, University Hospital of Örebro, Örebro, Sweden §Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany ∥Hologic Gen-Probe, San Diego, CA ¶Centre for Integrative Biology, University of Trento, Trento, Italy #Institute for Computational Biomedicine **Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors: Maria A
authors: MA
authors: Svensson
authors: Sven
authors: S
authors: Perner
authors: Anna-Lena
authors: AL
authors: Ohlson
authors: John R
authors: JR
authors: Day
authors: Jack
authors: J
authors: Groskopf
authors: Robert
authors: R
authors: Kirsten
authors: Thomas
authors: T
authors: Sollie
authors: Gisela
authors: G
authors: Helenius
authors: Swen-Olof
authors: SO
authors: Andersson
authors: Francesca
authors: F
authors: Demichelis
authors: Ove
authors: O
authors: Andrén
authors: Mark A
authors: MA
authors: Rubin
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001706:Biopsy; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000032:analysis; D005240:Feasibility Studies; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D013548:Sweden; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG
chemical_list: D000911:Antibodies, Monoclonal; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D004247:DNA