Faculty Collaboration Database

Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology 2012 Aug;119(8):1596-603

Date

04/24/2012

Pubmed ID

22521086

Pubmed Central ID

PMC3404209

DOI

10.1016/j.ophtha.2012.02.017

Scopus ID

2-s2.0-84864429034 (requires institutional sign-in at Scopus site)   385 Citations

Abstract

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.

Author List

Onken MD, Worley LA, Char DH, Augsburger JJ, Correa ZM, Nudleman E, Aaberg TM Jr, Altaweel MM, Bardenstein DS, Finger PT, Gallie BL, Harocopos GJ, Hovland PG, McGowan HD, Milman T, Mruthyunjaya P, Simpson ER, Smith ME, Wilson DJ, Wirostko WJ, Harbour JW

Author

William Wirostko MD Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Chromosomes, Human, Pair 3
Female
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Melanoma
Middle Aged
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Prognosis
Prospective Studies
Real-Time Polymerase Chain Reaction
Uveal Neoplasms
Young Adult