title: Higher percentage of FISH-determined monosomy 3 and 8q amplification in uveal melanoma cells relate to poor patient prognosis.
abstract: OBJECTIVE
  To investigate the relation between patient survival and incrementally increasing percentages of fluorescence in situ hybridization-determined complete loss of chromosome 3 (monosomy 3) and gain of chromosome 8q in primary uveal melanoma cells.
  
  
  METHODS
  Clinicopathological factors were related to disease-free survival. Fluorescence in situ hybridization was performed using probes on chromosomes 1, 3, 6, and 8. The percentages of UM cells with monosomy 3 or chromosome 8q gain were classified in groups with incrementally increasing percentages and related to disease-free survival. Correlations between clinical factors and cytogenetic aberrations were also analyzed.
  
  
  RESULTS
  Two-hundred twenty choroidal and ciliary body melanomas were analyzed. The following proved to be significant predictors of survival in univariate analysis: older patient age (P = 0.003); large tumor diameter (P < 0.001); mixed cell type (P = 0.001); presence of closed microvascular loops (P < 0.001); loss of chromosome 1p (P = 0.006); monosomy 3 (P < 0.001); gain of 6p (P < 0.001); and gain of chromosome 8q (P < 0.001). Multivariate Cox analysis displayed monosomy 3 (Hazard ratio [HR] 2.83, P = 0.002) and gain of chromosome 8q (HR 3.13, P = 0.002) as the most important independent prognostic factors of poor survival, followed by older patient age (HR 1.02, P = 0.017). Increasing percentages of monosomy 3 and gain of chromosome 8q in tumor cells showed a correlation with worse prognosis (Log-rank test 49.9 and 40.4, both P < 0.001) and increased number of additional copies of 8q correlated with shorter disease-free interval (Log-rank test 45.7, P < 0.001).
  
  
  CONCLUSIONS
  A high percentage monosomy 3 and chromosome 8q gain in primary UM cells showed a strong relation with poor disease-free survival compared with low percentage aberrations.
authors.affiliation: Department of Ocular Oncology, Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: van den Bosch
authors.forename: Jackelien G M
authors.initials: JG
authors.lastname: van Beek
authors.forename: Jolanda
authors.initials: J
authors.lastname: Vaarwater
authors.forename: Robert M
authors.initials: RM
authors.lastname: Verdijk
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Naus
authors.forename: Dion
authors.initials: D
authors.lastname: Paridaens
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.forename: Emine
authors.initials: E
authors.lastname: Kiliç
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D009006:Monosomy / Q000235:genetics*; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D014604:Uveal Neoplasms / Q000235:genetics* / Q000401:mortality; D055815:Young Adult; D000098943:Uveal Melanoma