title: Increased gene copy number of ERG on chromosome 21 but not TMPRSS2-ERG fusion predicts outcome in prostatic adenocarcinomas.
abstract: The role of TMPRSS2-ERG gene fusion in prostate cancer prognostication remains controversial. We evaluated the prognostic role of TMPRSS2-ERG fusion using fluorescence in situ hybridization analysis in a case-control study nested in The Johns Hopkins retropubic radical prostatectomy cohort. In all, 10 tissue microarrays containing paired tumors and normal tissues obtained from 172 cases (recurrence) and 172 controls (non-recurrence) matched on pathological grade, stage, race/ethnicity, and age at the time of surgery were analyzed. All radical prostatectomies were performed at our institution between 1993 and 2004. Recurrence was defined as biochemical recurrence, development of clinical evidence of metastasis, or death from prostate carcinoma. Each tissue microarray spot was scored for the presence of TMPRSS2-ERG gene fusion and for ERG gene copy number gains. The odds ratio of recurrence and 95% confidence intervals were estimated from conditional logistic regression. Although the percentage of cases with fusion was slightly lower in cases than in controls (50 vs 57%), the difference was not statistically significant (P=0.20). The presence of fusion due to either deletion or split event was not associated with recurrence. Similarly, the presence of duplicated ERG deletion, duplicated ERG split, or ERG gene copy number gain with a single ERG fusion was not associated with recurrence. ERG gene polysomy without fusion was significantly associated with recurrence (odds ratio 2.0, 95% confidence interval 1.17-3.42). In summary, TMPRSS2-ERG fusion was not prognostic for recurrence after retropubic radical prostatectomy for clinically localized prostate cancer, although men with ERG gene copy number gain without fusion were twice more likely to recur.
authors: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors: Antoun
authors: A
authors: Toubaji
authors: Roula
authors: R
authors: Albadine
authors: Alan K
authors: AK
authors: Meeker
authors: William B
authors: WB
authors: Isaacs
authors: Tamara
authors: T
authors: Lotan
authors: Michael C
authors: MC
authors: Haffner
authors: Alcides
authors: A
authors: Chaux
authors: Jonathan I
authors: JI
authors: Epstein
authors: Misop
authors: M
authors: Han
authors: Patrick C
authors: PC
authors: Walsh
authors: Alan W
authors: AW
authors: Partin
authors: Angelo M
authors: AM
authors: De Marzo
authors: Elizabeth A
authors: EA
authors: Platz
authors: George J
authors: GJ
authors: Netto
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000368:Aged; D015142:Baltimore; D016022:Case-Control Studies; D002891:Chromosomes, Human, Pair 21; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018570:Risk Assessment; D012307:Risk Factors; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D016896:Treatment Outcome
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG