PMID- 17332290 OWN - NLM STAT- MEDLINE DCOM- 20070509 LR - 20230208 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 13 IP - 5 DP - 2007 Mar 1 TI - Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma. PG - 1466-71 AB - PURPOSE: To compare a gene expression-based classifier versus the standard genetic prognostic marker, monosomy 3, for predicting metastasis in uveal melanoma. EXPERIMENTAL DESIGN: Gene expression profiling, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) were done on 67 primary uveal melanomas. Clinical and pathologic prognostic factors were also assessed. Variables were analyzed by Cox proportional hazards, Kaplan-Meier analysis, sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios. RESULTS: The gene expression-based molecular classifier assigned 27 tumors to class 1 (low risk) and 25 tumors to class 2 (high risk). By Cox univariate proportional hazards, class 2 signature (P = 0.0001), advanced patient age (P = 0.01), and scleral invasion (P = 0.007) were the only variables significantly associated with metastasis. Only the class 2 signature was needed to optimize predictive accuracy in a Cox multivariate model. A less significant association with metastasis was observed for monosomy 3 detected by aCGH (P = 0.076) and FISH (P = 0.127). The sensitivity and specificity for the molecular classifier (84.6% and 92.9%, respectively) were superior to monosomy 3 detected by aCGH (58.3% and 85.7%, respectively) and FISH (50.0% and 72.7%, respectively). Positive and negative predictive values (91.7% and 86.7%, respectively) and positive and negative likelihood ratios (11.9 and 0.2, respectively) for the molecular classifier were also superior to those for monosomy 3. CONCLUSIONS: Molecular classification based on gene expression profiling of the primary tumor was superior to monosomy 3 and clinicopathologic prognostic factors for predicting metastasis in uveal melanoma. FAU - Worley, Lori A AU - Worley LA AD - Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri 63110, USA. FAU - Onken, Michael D AU - Onken MD FAU - Person, Erica AU - Person E FAU - Robirds, Diane AU - Robirds D FAU - Branson, Julie AU - Branson J FAU - Char, Devron H AU - Char DH FAU - Perry, Arie AU - Perry A FAU - Harbour, J William AU - Harbour JW LA - eng GR - R01 CA125970/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Chromosomes, Human, Pair 3/genetics MH - Female MH - *Gene Expression Profiling/methods MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Melanoma/*genetics/*pathology MH - Middle Aged MH - Monosomy MH - Nucleic Acid Hybridization MH - Oligonucleotide Array Sequence Analysis MH - Predictive Value of Tests MH - Prognosis MH - Transcription, Genetic MH - Uveal Neoplasms/*genetics/*pathology EDAT- 2007/03/03 09:00 MHDA- 2007/05/10 09:00 CRDT- 2007/03/03 09:00 PHST- 2007/03/03 09:00 [pubmed] PHST- 2007/05/10 09:00 [medline] PHST- 2007/03/03 09:00 [entrez] AID - 13/5/1466 [pii] AID - 10.1158/1078-0432.CCR-06-2401 [doi] PST - ppublish SO - Clin Cancer Res. 2007 Mar 1;13(5):1466-71. doi: 10.1158/1078-0432.CCR-06-2401.