Prognostic significance of chromosome 3 alterations determined by microsatellite analysis in uveal melanoma: a long-term follow-up study

Br J Cancer. 2012 Mar 13;106(6):1171-6. doi: 10.1038/bjc.2012.54. Epub 2012 Feb 21.


Background: In uveal melanoma (UM), the most frequent primary intraocular tumour in adults, loss of one entire chromosome 3 (monosomy 3 (M3)) is observed in ~50% of tumours and is significantly associated with metastatic disease. The strong association of metastatic disease with M3 offers the opportunity for molecular prognostic testing of UM patients.

Methods: To re-evaluate M3 as prognostic marker in our clinical and laboratory setting and to determine the metastatic potential of rare tumours with partial M3, we performed a comprehensive study on 374 UM patients treated by enucleation in our clinic within 10 consecutive years, starting in 1998. Genotyping of all tumours was performed by microsatellite analysis.

Results: Median follow-up time was 5.2 years. The disease-specific mortality rates (death by UM metastases) for tumours with disomy 3 (D3) and M3 were 13.2% and 75.1%, respectively. The disease-specific survival was worse when M3 was observed together with chromosome 8 alterations (P=0.020). Death of UM metastases was also observed in 12 patients (9%) with D3 tumours. The metastasising D3 tumours showed a larger basal tumour diameter (P=0.007), and were more frequently of mixed or epitheloid cell type (P<0.0001) than D3 tumours that did not metastasise. Mortality rate of tumours showing partial M3 (8.3%) was as low as that for tumours with D3.

Conclusion: This shows that large tumours with disomy 3 have an increased risk to develop metastases. On the basis of these results, our clinic offers routine prognostic testing of UM patients by chromosome 3 typing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Chromosomes, Human, Pair 3*
  • Chromosomes, Human, Pair 8
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / diagnosis*
  • Melanoma / genetics
  • Melanoma / mortality
  • Melanoma / secondary
  • Microsatellite Repeats*
  • Middle Aged
  • Monosomy*
  • Prognosis
  • Proportional Hazards Models
  • Tumor Burden
  • Uveal Neoplasms / diagnosis*
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / mortality
  • Uveal Neoplasms / pathology


  • Biomarkers, Tumor