title: Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma.
abstract: OBJECTIVE
  This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk).
  
  
  METHODS
  Prospective, multicenter study.
  
  
  METHODS
  A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers.
  
  
  METHODS
  Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status.
  
  
  METHODS
  Patients were managed for their primary tumor and monitored for metastasis.
  
  
  RESULTS
  The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status.
  
  
  CONCLUSIONS
  The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.
authors.affiliation: Washington University and Siteman Cancer Center, St. Louis, Missouri, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Onken
authors.forename: Lori A
authors.initials: LA
authors.lastname: Worley
authors.forename: Devron H
authors.initials: DH
authors.lastname: Char
authors.forename: James J
authors.initials: JJ
authors.lastname: Augsburger
authors.forename: Zelia M
authors.initials: ZM
authors.lastname: Correa
authors.forename: Eric
authors.initials: E
authors.lastname: Nudleman
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Aaberg
authors.forename: Michael M
authors.initials: MM
authors.lastname: Altaweel
authors.forename: David S
authors.initials: DS
authors.lastname: Bardenstein
authors.forename: Paul T
authors.initials: PT
authors.lastname: Finger
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Gallie
authors.forename: George J
authors.initials: GJ
authors.lastname: Harocopos
authors.forename: Peter G
authors.initials: PG
authors.lastname: Hovland
authors.forename: Hugh D
authors.initials: HD
authors.lastname: McGowan
authors.forename: Tatyana
authors.initials: T
authors.lastname: Milman
authors.forename: Prithvi
authors.initials: P
authors.lastname: Mruthyunjaya
authors.forename: E Rand
authors.initials: ER
authors.lastname: Simpson
authors.forename: Morton E
authors.initials: ME
authors.lastname: Smith
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.forename: William J
authors.initials: WJ
authors.lastname: Wirostko
authors.forename: J William
authors.initials: JW
authors.lastname: Harbour
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D014604:Uveal Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor