Prognostication in Choroidal Melanoma

  • Sarah E. Coupland
  • Azzam Taktak
  • Antonio Eleuteri
  • Helen Kalirai
  • Bertil Damato


Without timely treatment, uveal melanomas (UM) make the affected eye blind and painful. Despite successful ocular treatment, about 50 % of UM patients develop metastatic disease, which usually involves the liver. Treatment of metastases only rarely prolongs life. Most patients die within a year of onset of symptomatic metastases. It is hoped that such metastatic disease may be delayed or prevented by systemic adjuvant therapy administered soon after treatment of the primary ocular tumor. This approach would require identification of high-risk patients, that is, individuals who are likely to have micrometastases by the time their primary ocular tumor is detected and treated.


Uveal Melanoma Systemic Adjuvant Therapy Choroidal Melanoma Uveal Melanoma Cell Uveal Melanoma Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Damato B. Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye (Lond). 2012;26(9):1157–72.CrossRefGoogle Scholar
  2. 2.
    Frenkel S, Nir I, Hendler K, et al. Long-term survival of uveal melanoma patients after surgery for liver metastases. Br J Ophthalmol. 2009;93(8):1042–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Mariani P, Servois V, Piperno-Neumann S. Therapeutic options in metastatic uveal melanoma. Dev Ophthalmol. 2011;49:166–81.PubMedCrossRefGoogle Scholar
  4. 4.
    Kujala E, Makitie T, Kivela T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci. 2003;44(11):4651–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Whitehead J, Tishkovskaya S, O'Connor J, Damato B. Devising two-stage and multistage phase II studies on systemic adjuvant therapy for uveal melanoma. Invest Ophthalmol Vis Sci. 2012;53(8):4986–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Damato B, Duke C, Coupland SE, et al. Cytogenetics of uveal melanoma: a 7-year clinical experience. Ophthalmology. 2007;114(10):1925–31.PubMedCrossRefGoogle Scholar
  7. 7.
    Damato BE, Coupland SE. Differences in uveal melanomas between men and women from the British Isles. Eye (Lond). 2011;26(2):292–9.CrossRefGoogle Scholar
  8. 8.
    Damato B, Eleuteri A, Taktak AF, Coupland SE. Estimating prognosis for survival after treatment of choroidal melanoma. Prog Retin Eye Res. 2011;30(5):285–95.PubMedCrossRefGoogle Scholar
  9. 9.
    Khan S, Finger PT, Yu GP, et al. Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study. Arch Ophthalmol. 2011;130(1):57–64.PubMedCrossRefGoogle Scholar
  10. 10.
    Kivela T, Kujala E. Prognostication in eye cancer: the latest tumor, node, metastasis classification and beyond. Eye (Lond). 2013;27(2):243–52.CrossRefGoogle Scholar
  11. 11.
    Eleuteri A, Damato B, Coupland SE, Taktak A. Enhancing survival prognostication in patients with choroidal melanoma by integrating pathologic, clinical and genetic predictors of metastasis. Int J Biomed Eng Technol. 2012;8:18–35.CrossRefGoogle Scholar
  12. 12.
    Prescher G, Bornfeld N, Becher R. Nonrandom chromosomal abnormalities in primary uveal melanoma. J Natl Cancer Inst. 1990;82(22):1765–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Sisley K, Cottam DW, Rennie IG, et al. Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma. Genes Chromosomes Cancer. 1992;5(3):197–200.PubMedCrossRefGoogle Scholar
  14. 14.
    Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel KH, Becher R. Prognostic implications of monosomy 3 in uveal melanoma. Lancet. 1996;347(9010):1222–5.PubMedCrossRefGoogle Scholar
  15. 15.
    White VA, Chambers JD, Courtright PD, Chang WY, Horsman DE. Correlation of cytogenetic abnormalities with the outcome of patients with uveal melanoma. Cancer. 1998;83(2):354–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Damato B, Dopierala JA, Coupland SE. Genotypic profiling of 452 choroidal melanomas with multiplex ligation-dependent probe amplification. Clin Cancer Res. 2010;16(24):6083–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Damato B, Dopierala J, Klaasen A, van Dijk M, Sibbring J, Coupland SE. Multiplex ligation-dependent probe amplification of uveal melanoma: correlation with metastatic death. Invest Ophthalmol Vis Sci. 2009;50(7):3048–55.PubMedCrossRefGoogle Scholar
  18. 18.
    Coupland SE, Kalirai H, Baudo M, Maye U, Zeschnigk M, Damato B. Quality assessment of multiplex ligation-dependent probe amplification (MLPA) in uveal melanoma by comparison with array comparative genomic hybridization (aCGH) and microsatellite analysis (MSA). ARVO Abstract. 2012.Google Scholar
  19. 19.
    Hömig-Hölzel C, Savola S. Multiplex ligation-dependent probe amplification (MLPA) in tumor diagnostics and prognostics. Diagn Mol Pathol. 2012;21(4):189–206.PubMedCrossRefGoogle Scholar
  20. 20.
    Schwab CJ, Jones LR, Morrison H, et al. Evaluation of multiplex ligation-dependent probe amplification as a method for the detection of copy number abnormalities in B-cell precursor acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2010;49(12):1104–13.PubMedCrossRefGoogle Scholar
  21. 21.
    Sisley K, Nichols C, Parsons MA, Farr R, Rees RC, Rennie IG. Clinical applications of chromosome analysis, from fine needle aspiration biopsies, of posterior uveal melanomas. Eye (Lond). 1998;12(Pt 2):203–7.CrossRefGoogle Scholar
  22. 22.
    Bonaldi L, Midena E, Filippi B, et al. FISH analysis of chromosomes 3 and 6 on fine needle aspiration biopsy samples identifies distinct subgroups of uveal melanomas. J Cancer Res Clin Oncol. 2008;134(10):1123–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Midena E, Bonaldi L, Parrozzani R, Radin PP, Boccassini B, Vujosevic S. In vivo monosomy 3 detection of posterior uveal melanoma: 3-year follow-up. Graefes Arch Clin Exp Ophthalmol. 2008;246(4):609–14.PubMedCrossRefGoogle Scholar
  24. 24.
    Singh AD, Aronow ME, Sun Y, et al. Chromosome 3 status in uveal melanoma: a comparison of fluorescence in situ hybridization and single-nucleotide polymorphism array. Invest Ophthalmol Vis Sci. 2012;53(7):3331–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Gordon KB, Thompson CT, Char DH, et al. Comparative genomic hybridization in the detection of DNA copy number abnormalities in uveal melanoma. Cancer Res. 1994;54(17):4764–8.PubMedGoogle Scholar
  26. 26.
    Speicher MR, Prescher G, du Manoir S, et al. Chromosomal gains and losses in uveal melanomas detected by comparative genomic hybridization. Cancer Res. 1994;54(14):3817–23.PubMedGoogle Scholar
  27. 27.
    Ghazvini S, Char DH, Kroll S, Waldman FM, Pinkel D. Comparative genomic hybridization analysis of archival formalin-fixed paraffin-embedded uveal melanomas. Cancer Genet Cytogenet. 1996;90(2):95–101.PubMedCrossRefGoogle Scholar
  28. 28.
    Aalto Y, Eriksson L, Seregard S, Larsson O, Knuutila S. Concomitant loss of chromosome 3 and whole arm losses and gains of chromosome 1, 6, or 8 in metastasizing primary uveal melanoma. Invest Ophthalmol Vis Sci. 2001;42(2):313–7.PubMedGoogle Scholar
  29. 29.
    Hughes S, Damato BE, Giddings I, Hiscott PS, Humphreys J, Houlston RS. Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3. Br J Cancer. 2005;93(10):1191–6.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Kilic E, van Gils W, Lodder E, et al. Clinical and cytogenetic analyses in uveal melanoma. Invest Ophthalmol Vis Sci. 2006;47(9):3703–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Ehlers JP, Worley L, Onken MD, Harbour JW. Integrative genomic analysis of aneuploidy in uveal melanoma. Clin Cancer Res. 2008;14(1):115–22.PubMedGoogle Scholar
  32. 32.
    Petrausch U, Martus P, Tonnies H, et al. Significance of gene expression analysis in uveal melanoma in comparison to standard risk factors for risk assessment of subsequent metastases. Eye (Lond). 2008;22(8):997–1007.CrossRefGoogle Scholar
  33. 33.
    Vaarwater J, van den Bosch T, Mensink HW, et al. Multiplex ligation-dependent probe amplification equals fluorescence in-situ hybridization for the identification of patients at risk for metastatic disease in uveal melanoma. Melanoma Res. 2011;22(1):30–7.Google Scholar
  34. 34.
    Shields CL, Ganguly A, Bianciotto CG, Turaka K, Tavallali A, Shields JA. Prognosis of uveal melanoma in 500 cases using genetic testing of fine-needle aspiration biopsy specimens. Ophthalmology. 2010;118(2):396–401.CrossRefGoogle Scholar
  35. 35.
    Thomas S, Putter C, Weber S, Bornfeld N, Lohmann DR, Zeschnigk M. Prognostic significance of chromosome 3 alterations determined by microsatellite analysis in uveal melanoma: a long-term follow-up study. Br J Cancer. 2012;106(6):1171–6.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Onken MD, Worley LA, Person E, Char DH, Bowcock AM, Harbour JW. Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma. Clin Cancer Res. 2007;13(10):2923–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Trolet J, Hupe P, Huon I, et al. Genomic profiling and identification of high-risk uveal melanoma by array CGH analysis of primary tumors and liver metastases. Invest Ophthalmol Vis Sci. 2009;50(6):2572–80.PubMedCrossRefGoogle Scholar
  38. 38.
    McCannel TA, Burgess BL, Nelson SF, Eskin A, Straatsma BR. Genomic identification of significant targets in ciliochoroidal melanoma. Invest Ophthalmol Vis Sci. 2010;52(6):3018–22.CrossRefGoogle Scholar
  39. 39.
    Onken MD, Worley LA, Tuscan MD, Harbour JW. An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma. J Mol Diagn. 2010;12(4):461–8.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Onken MD, Worley LA, Char DH, et al. Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology. 2012;119(8):1596–603.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Harbour JW, Onken MD, Roberson ED, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330(6009):1410–3.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Taktak AF, Fisher AC, Damato BE. Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem. Phys Med Biol. 2004;49(1):87–98.PubMedGoogle Scholar
  43. 43.
    Eleuteri A, Aung MS, Taktak AF, Damato B, Lisboa PJ. Continuous and discrete time survival analysis: neural network approaches. Conf Proc IEEE Eng Med Biol Soc. 2007;2007:5420–3.PubMedGoogle Scholar
  44. 44.
    Damato B, Eleuteri A, Fisher AC, Coupland SE, Taktak AF. Artificial neural networks estimating survival probability after treatment of choroidal melanoma. Ophthalmology. 2008;115(9):1598–607.PubMedCrossRefGoogle Scholar
  45. 45.
    Harrell F. Parametric survival models. In: Regression modeling strategies. Heidelberg: Springer; 2001. p. 413–41.CrossRefGoogle Scholar
  46. 46.
    Cook SA, Damato B, Marshall E, Salmon P. Psychological aspects of cytogenetic testing of uveal melanoma: preliminary findings and directions for future research. Eye (Lond). 2009;23(3):581–5.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sarah E. Coupland
    • 1
  • Azzam Taktak
    • 2
  • Antonio Eleuteri
    • 2
  • Helen Kalirai
    • 1
  • Bertil Damato
    • 3
  1. 1.Department of Molecular and Clinical Cancer Medicine, Institute of Translational MedicineUniversity of LiverpoolLiverpoolUK
  2. 2.Department of Clinical EngineeringRoyal Liverpool University HospitalLiverpoolUK
  3. 3.Ocular Oncology Service, Departments of Ophthalmology and Ocular OncologyUniversity of California San FranciscoSan FranciscoUSA

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