title: TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma.
abstract: Minute prostatic adenocarcinomas are considered to be of insufficient virulence. Given recent suggestions of TMPRSS2-ERG gene fusion association with aggressive prostatic adenocarcinoma, we evaluated the incidence of TMPRSS2-ERG fusion in minute prostatic adenocarcinomas. A total of 45 consecutive prostatectomies with minute adenocarcinoma were used for tissue microarray construction. A total of 63 consecutive non-minimal, Gleason Score 6 tumors, from a separate PSA Era prostatectomy tissue microarray, were used for comparison. FISH was carried out using ERG break-apart probes. Tumors were assessed for fusion by deletion (Edel) or split (Esplit), duplicated fusions and low-level copy number gain in normal ERG gene locus. Minute adenocarcinomas: Fusion was evaluable in 32/45 tumors (71%). Fifteen out of 32 (47%) tumors were positive for fusion. Six (19%) were of the Edel class and 7 (22%) were classified as combined Edel+Esplit. Non-minute adenocarcinomas (pT2): Fusion was identified in 20/30 tumors (67%). Four (13%) were of Edel class and 5 (17%) were combined Edel+Esplit. Duplicated fusions were encountered in 5 (16%) tumors. Non-minute adenocarcinomas (pT3): Fusion was identified in 19/33 (58%). Fusion was due to a deletion in 6 (18%) tumors. Seven tumors (21%) were classified as combined Edel+Esplit. One tumor showed Esplit alone. Duplicated fusions were encountered in 3 (9%) cases. The incidence of duplicated fusions was higher in non-minute adenocarcinomas (13 vs 0%; P=0.03). A trend for higher incidence of low-level copy number gain in normal ERG gene locus without fusion was noted in non-minute adenocarcinomas (10 vs 0%; P=0.07). We found a TMPRSS2-ERG fusion rate of 47% in minute adenocarcinomas. The latter is not significantly different from that of grade matched non-minute adenocarcinomas. The incidence of duplicated fusion was higher in non-minute adenocarcinomas. Our finding of comparable rate of TMPRSS2-ERG fusion in minute adenocarcinomas may argue against its value as a marker of aggressive prostate carcinoma phenotype.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Roula
authors.initials: R
authors.lastname: Albadine
authors.forename: Mathieu
authors.initials: M
authors.lastname: Latour
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Michael
authors.initials: M
authors.lastname: Haffner
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Elizabeth
authors.initials: E
authors.lastname: A Platz
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Demarzo
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D050596:Oncogene Fusion / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D012697:Serine Endopeptidases / Q000235:genetics*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human