title: Effect of heterogeneous distribution of monosomy 3 on prognosis in uveal melanoma.
abstract: BACKGROUND
  Fluorescence in situ hybridization (FISH) analyses on tumor sections and on isolated nuclei showed that even low numbers of cells with monosomy of chromosome 3 adversely affected survival.
  
  
  OBJECTIVE
  To determine what percentage of uveal melanoma cells with monosomy of chromosome 3 influences patient mortality.
  
  
  METHODS
  To determine the presence of monosomy 3, karyotyping and FISH on cultured cells and FISH on isolated nuclei were performed on 50 primary uveal melanomas. Clinical and pathologic prognostic factors were assessed and compared with 5-year survival data. Analyses were performed using Cox proportional hazards test, log-rank analysis, sensitivity, specificity, and positive and negative likelihood ratios.
  
  
  RESULTS
  Combined karyotyping and FISH on cultured cells showed monosomy 3 in 19 of 50 cases (38%), whereas determination of the monosomy 3 status by FISH on isolated nuclei with a threshold of 5% assigned 31 of 50 cases (62%) to the monosomy-3 category. When monosomy 3 on isolated nuclei with a cutoff value of 5% was used, a significant difference in 5-year survival was present (hazard ratio, 15.5; P = .007), indicating that monosomy 3 in greater than 5% of tumor cells is related to death due to metastases.
  
  
  CONCLUSIONS
  In uveal melanoma, the presence of greater than 5% of cells with monosomy 3, as determined by FISH on isolated nuclei, is associated with the development of metastases within 5 years after enucleation.
authors.affiliation: Department of Ophthalmology, Leiden University Medical Center, the Netherlands.
authors.forename: Inge H G
authors.initials: IH
authors.lastname: Bronkhorst
authors.forename: Willem
authors.initials: W
authors.lastname: Maat
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Jordanova
authors.forename: Wilma G M
authors.initials: WG
authors.lastname: Kroes
authors.forename: Nicoline E
authors.initials: NE
authors.lastname: Schalij-Delfos
authors.forename: Gregorius P M
authors.initials: GP
authors.lastname: Luyten
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Jager
mesh_terms: D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008875:Middle Aged; D009006:Monosomy; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery
chemical_list: D004273:DNA, Neoplasm