Higher percentage of FISH-determined monosomy 3 and 8q amplification in uveal melanoma cells relate to poor patient prognosis

Thomas van den Bosch, Jackelien G M van Beek, Jolanda Vaarwater, Robert M Verdijk, Nicole C Naus, Dion Paridaens, Annelies de Klein, Emine Kiliç

Research output: Contribution to journalArticleResearchpeer-review

Abstract

PURPOSE: 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.

Original languageEnglish
Pages (from-to)2668-74
Number of pages7
JournalInvestigative ophthalmology & visual science
Volume53
Issue number6
DOIs
Publication statusPublished - 14 May 2012

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosomes, Human, Pair 3/genetics
  • Chromosomes, Human, Pair 8/genetics
  • Disease-Free Survival
  • Female
  • Gene Amplification
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Melanoma/genetics
  • Middle Aged
  • Monosomy/genetics
  • Multivariate Analysis
  • Prognosis
  • Risk Factors
  • Survival Analysis
  • Uveal Neoplasms/genetics
  • Young Adult

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