Document Detail

Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma.
MedLine Citation:
PMID:  22521086     Owner:  NLM     Status:  MEDLINE    
PURPOSE: 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).
DESIGN: Prospective, multicenter study.
PARTICIPANTS: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers.
TESTING: 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.
MAIN OUTCOME MEASURES: 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.
Michael D Onken; Lori A Worley; Devron H Char; James J Augsburger; Zelia M Correa; Eric Nudleman; Thomas M Aaberg; Michael M Altaweel; David S Bardenstein; Paul T Finger; Brenda L Gallie; George J Harocopos; Peter G Hovland; Hugh D McGowan; Tatyana Milman; Prithvi Mruthyunjaya; E Rand Simpson; Morton E Smith; David J Wilson; William J Wirostko; J William Harbour
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Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2012-04-21
Journal Detail:
Title:  Ophthalmology     Volume:  119     ISSN:  1549-4713     ISO Abbreviation:  Ophthalmology     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-03     Completed Date:  2012-10-25     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  7802443     Medline TA:  Ophthalmology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1596-603     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Aged, 80 and over
Chromosomes, Human, Pair 3 / genetics
Follow-Up Studies
Gene Expression Profiling*
Gene Expression Regulation, Neoplastic / physiology
Melanoma / genetics*,  pathology
Middle Aged
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Prospective Studies
Real-Time Polymerase Chain Reaction
Tumor Markers, Biological / genetics*
Uveal Neoplasms / genetics*,  pathology
Young Adult
Grant Support
P30 EY02687C/EY/NEI NIH HHS; R01 CA125970/CA/NCI NIH HHS; R01 CA125970/CA/NCI NIH HHS; R01 CA125970-06/CA/NCI NIH HHS
Reg. No./Substance:
0/Tumor Markers, Biological
Comment In:
Ophthalmology. 2013 Jul;120(7):e51   [PMID:  23823529 ]
Ophthalmology. 2013 Jul;120(7):e50   [PMID:  23823528 ]
Ophthalmology. 2013 May;120(5):1109.e1   [PMID:  23642753 ]
Ophthalmology. 2013 Jul;120(7):e52-3   [PMID:  23823531 ]

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