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Uveal Melanoma: Prognostication Methods

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Clinical Ophthalmic Oncology

Abstract

Almost 50% of uveal melanoma (UM) patients develop metastatic disease, despite successful ocular treatment. Metastases usually involve the liver and only rarely respond to treatment so that most patients die within a year of onset of symptoms. There are hopes that systemic adjuvant therapy may delay or prevent metastatic disease. This requires targeting of high-risk patients, according to anatomic, histologic, and genetic predictors. Metastatic disease occurs almost exclusively in patients whose tumor shows genetic aberrations such as chromosome 3 loss, chromosome 8q gains, and BAP1 mutation. The detection of lethal genetic aberrations has become more sensitive with the development of methods such as comparative genomic hybridization, microsatellite analysis, multiplex ligation-dependent probe amplification, single-nucleotide polymorphisms, gene expression profiling, next-generation sequencing, and immunohistochemical analysis of nuclear BAP1 expression. The time from ocular treatment to the onset of metastatic disease tends to be shorter in patients with a larger, more extensive ocular tumor and a higher grade of malignancy as evidenced by epithelioid cytomorphology and higher mitotic count. Ideally, prognostication is performed by multivariable analysis using a tool such as the Liverpool Uveal Melanoma Prognosticator Online (LUMPO). Accurate prognostication enhances quality of life, especially in patients with a good prognosis. It also allows targeting of systemic surveillance and systemic adjuvant therapy in high-risk patients and enhances opportunities for research.

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References

  1. Damato B. Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye. 2012;26(9):1157–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  3. Mariani P, Servois V, Piperno-Neumann S. Therapeutic options in metastatic uveal melanoma. current concepts in uveal melanoma. Basel: KARGER; 2011.

    Chapter  Google Scholar 

  4. Kujala E, Ma¨kitie T, Kivela¨ T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Opthalmol Visual Science. 2003;44(11):4651.

    Article  Google Scholar 

  5. Whitehead J, Tishkovskaya S, O’Connor J, et al. Devising two-stage and multistage phase II studies on systemic adjuvant therapy for uveal melanoma. Invest Opthalmol Vis Sci. 2012;53(8):4986.

    Article  CAS  Google Scholar 

  6. Damato B, Duke C, Coupland SE, et al. Cytogenetics of uveal melanoma. Ophthalmology. 2007;114(10):1925–31. e1.

    Article  PubMed  Google Scholar 

  7. Damato BE, Coupland SE. Differences in uveal melanomas between men and women from the British Isles. Eye. 2011;26(2):292–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Damato B, Eleuteri A, Taktak AFG, et al. Estimating prognosis for survival after treatment of choroidal melanoma. Prog Retin Eye Res. 2011;30(5):285–95.

    Article  PubMed  Google Scholar 

  9. Khan S. Clinical and pathologic characteristics of biopsy-proven Iris melanoma. Arch Ophthalmol. 2012;130(1):57.

    Article  PubMed  Google Scholar 

  10. Scholz SL, Moller I, Reis H, et al. Frequent GNAQ, GNA11, and EIF1AX mutations in Iris melanoma. Invest Ophthalmol Vis Sci. 2017;58(9):3464–70.

    Article  CAS  PubMed  Google Scholar 

  11. Harbour JW, Wilson D, Finger PT, et al. Gene expressing profiling of iris melanomas. Ophthalmology. 2013;120(1):213, e1-3.

    Article  Google Scholar 

  12. Krishna Y, Kalirai H, Thornton S, et al. Genetic findings in treatment-naive and proton-beam-radiated iris melanomas. Br J Ophthalmol. 2016;100(7):1012–6.

    Article  PubMed  Google Scholar 

  13. Kivelä T, Kujala E. Prognostication in eye cancer: the latest tumor, node, metastasis classification and beyond. Eye. 2012;27(2):243–52.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Dogrusoz M, Bagger M, van Duinen SG, et al. The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status. Invest Ophthalmol Vis Sci. 2017;58(2):833–42.

    Article  PubMed  Google Scholar 

  15. Eleuteri A, Damato B, Coupland SE, et al. Enhancing survival prognostication in patients with choroidal melanoma by integrating pathologic, clinical and genetic predictors of metastasis. Int J Biomed Eng Technol. 2012;8(1):18.

    Article  Google Scholar 

  16. Prescher G, Bornfeld N, Becher R. Nonrandom chromosomal abnormalities in primary uveal melanoma. JNCI: J Nat Cancer Inst. 1990;82(22):1765–9.

    Article  CAS  PubMed  Google Scholar 

  17. Prescher G, Speicher MR, du Manoir S, et al. Comparative genomic hybridization of uveal melanoma. Cancer Genet Cytogenet. 1994;77(2):163.

    Article  Google Scholar 

  18. Sisley K, Cottam DW, Rennie IG, et al. Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma. Genes Chromosom Cancer. 1992;5(3):197–200.

    Article  CAS  PubMed  Google Scholar 

  19. White VA, Chambers JD, Courtright PD, et al. Correlation of cytogenetic abnormalities with the outcome of patients with uveal melanoma. Cancer. 1998;83(2):354–9.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. Damato B, Dopierala J, Klaasen A, et al. Multiplex ligation-dependent probe amplification of uveal melanoma: correlation with metastatic death. Invest Opthalmol Vis Sci. 2009;50(7):3048.

    Article  Google Scholar 

  22. Coupland SE, Kalirai H, Baudo M, et al. Quality assessment of multiplex ligation-dependent probe amplification (mlpa) in uveal melanoma by comparison witha array comparative genomic hybridization (acgh) and microsatellite analysis (msa). Invest Ophthalmol Vis Sci. 2012;53(14):5252.

    Google Scholar 

  23. Hömig-Hölzel C, Savola S. Multiplex ligation-dependent probe amplification (MLPA) in tumor diagnostics and prognostics. Diagn Mol Pathol. 2012;21(4):189–206.

    Article  PubMed  CAS  Google Scholar 

  24. 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 Chromosom Cancer. 2010;49(12):1104–13.

    Article  CAS  PubMed  Google Scholar 

  25. Sisley K, Nichols C, Parsons MA, et al. Clinical applications of chromosome analysis, from fine needle aspiration biopsies, of posterior uveal melanomas. Eye. 1998;12(2):203–7.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  CAS  PubMed  Google Scholar 

  27. Midena E, Bonaldi L, Parrozzani R, et al. In vivo monosomy 3 detection of posterior uveal melanoma: 3-year follow-up. Graefes Arch Clin Exp Ophthalmol. 2007;246(4):609–14.

    Article  PubMed  Google Scholar 

  28. 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 Opthalmol Vis Sci. 2012;53(7):3331.

    Article  CAS  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. 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.

    CAS  PubMed  Google Scholar 

  31. Ghazvini S, Char DH, Kroll S, et al. Comparative genomic hybridization analysis of archival formalin-fixed paraffin-embedded uveal melanomas. Cancer Genet Cytogenet. 1996;90(2):95–101.

    Article  CAS  PubMed  Google Scholar 

  32. Aalto Y, Eriksson L, Seregard S, et al. 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.

    CAS  PubMed  Google Scholar 

  33. Hughes S, Damato BE, Giddings I, et al. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kilic E, van Gils W, Lodder E, et al. Clinical and cytogenetic analyses in uveal melanoma. Invest Opthalmol Vis Sci. 2006;47(9):3703.

    Article  Google Scholar 

  35. Ehlers JP, Worley L, Onken MD, et al. Integrative genomic analysis of aneuploidy in uveal melanoma. Clin Cancer Res. 2008;14(1):115–22.

    Article  CAS  PubMed  Google Scholar 

  36. Petrausch U, Martus P, Tönnies H, et al. Significance of gene expression analysis in uveal melanoma in comparison to standard risk factors for risk assessment of subsequent metastases. Eye. 2007;22(8):997–1007.

    Article  PubMed  CAS  Google Scholar 

  37. 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. 2012;22(1):30–7.

    Article  CAS  PubMed  Google Scholar 

  38. Shields CL, Ganguly A, Bianciotto CG, et al. Prognosis of uveal melanoma in 500 cases using genetic testing of fine-needle aspiration biopsy specimens. Ophthalmology. 2011;118(2):396–401.

    Article  PubMed  Google Scholar 

  39. Thomas S, Pütter C, Weber S, et al. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Onken MD, Worley LA, Person E, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  41. Dogrusoz M, Jager MJ. Genetic prognostication in uveal melanoma. Acta Ophthalmol. 2018;96(4):331–47.

    Article  PubMed  Google Scholar 

  42. Onken MD, Worley LA, Tuscan MD, et al. An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma. J Mol Diagn. 2010;12(4):461–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 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.

    Article  PubMed  Google Scholar 

  44. Field MG, Decatur CL, Kurtenbach S, et al. PRAME as an independent biomarker for metastasis in uveal melanoma. Clin Cancer Res. 2016;22(5):1234–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Harbour JW, Onken MD, Roberson ED, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330(6009):1410–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Koopmans AE, Verdijk RM, Brouwer RW, et al. Clinical significance of immunohistochemistry for detection of BAP1 mutations in uveal melanoma. Mod Pathol. 2014;27(10):1321–30.

    Article  CAS  PubMed  Google Scholar 

  47. Shah AA, Bourne TD, Murali R. BAP1 protein loss by immunohistochemistry: a potentially useful tool for prognostic prediction in patients with uveal melanoma. Pathology. 2013;45(7):651–6.

    Article  CAS  PubMed  Google Scholar 

  48. Kalirai H, Dodson A, Faqir S, et al. Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing. Br J Cancer. 2014;111(7):1373–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. van de Nes JA, Nelles J, Kreis S, et al. Comparing the prognostic value of BAP1 mutation pattern, chromosome 3 status, and BAP1 immunohistochemistry in uveal melanoma. Am J Surg Pathol. 2016;40(6):796–805.

    Article  PubMed  Google Scholar 

  50. Farquhar N, Thornton S, Coupland SE, et al. Patterns of BAP1 protein expression provide insights into prognostic significance and the biology of uveal melanoma. J Pathol Clin Res. 2018;4(1):26–38.

    Article  CAS  PubMed  Google Scholar 

  51. Martin M, Masshofer L, Temming P, et al. Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet. 2013;45(8):933–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Royer-Bertrand B, Torsello M, Rimoldi D, et al. Comprehensive genetic landscape of uveal melanoma by whole-genome sequencing. Am J Hum Genet. 2016;99(5):1190–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Robertson AG, Shih J, Yau C, et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell. 2017;32(2):204–20 e15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Reiman A, Kikuchi H, Scocchia D, et al. Validation of an NGS mutation detection panel for melanoma. BMC Cancer. 2017;17(1):150.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Smit KN, van Poppelen NM, Vaarwater J, et al. Combined mutation and copy-number variation detection by targeted next-generation sequencing in uveal melanoma. Mod Pathol. 2018;31(5):763–71.

    Article  CAS  PubMed  Google Scholar 

  56. Bellerive C, Binkley E, Singh AD. Class 2 gene expression profile of a hemorrhagic pigment epithelial detachment misdiagnosed as melanoma. Ophthalmol Retina. 2019;3(5):453–5.

    Article  PubMed  Google Scholar 

  57. Klufas MA, Itty S, McCannel CA, et al. Variable results for uveal melanoma-specific gene expression profile prognostic test in choroidal metastasis. JAMA Ophthalmol. 2015;133(9):1073–6.

    Article  PubMed  Google Scholar 

  58. Klufas MA, Richter E, Itty S, et al. Comparison of gene expression profiling and chromosome 3 analysis by fluorescent in situ hybridization and multiplex ligation probe amplification in fine-needle aspiration biopsy specimens of uveal melanoma. Ocul Oncol Pathol. 2017;4(1):16–20.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Bellerive C, Grossniklaus HE, Singh AD. Prognostication for uveal melanoma: are two tests better than one? Ocul Oncol Pathol. 2017;3(4):301–3.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Shao YF, Echegaray JJ, Singh N, et al. Variability of bad prognosis in uveal melanoma. Ophthalmol Retina. 2019;3(2):186–93.

    Article  PubMed  Google Scholar 

  61. Taktak AFG, Fisher AC, Damato BE. Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem. Phys Med Biol. 2003;49(1):87–98.

    Article  Google Scholar 

  62. Eleuteri A, Aung MSH, Taktak AFG, et al. Continuous and discrete time survival analysis: neural network approaches. 2007 29th annual international conference of the IEEE engineering in medicine and biology society: IEEE; 2007.

    Google Scholar 

  63. Damato B, Eleuteri A, Fisher AC, et al. Artificial neural networks estimating survival probability after treatment of choroidal melanoma. Ophthalmology. 2008;115(9):1598–607.

    Article  PubMed  Google Scholar 

  64. Harrell FE. Parametric survival models. Regression modeling strategies: Springer International Publishing; 2015.

    Chapter  Google Scholar 

  65. Eleuteri A, Taktak AFG, Coupland SE, et al. Prognostication of metastatic death in uveal melanoma patients: a Markov multi-state model. Comput Biol Med. 2018;102:151–6.

    Article  PubMed  Google Scholar 

  66. DeParis SW, Taktak A, Eleuteri A, et al. External validation of the liverpool uveal melanoma prognosticator online. Invest Ophthalmol Vis Sci. 2016;57(14):6116–22.

    Article  PubMed  Google Scholar 

  67. Vaquero-Garcia J, Lalonde E, Ewens KG, et al. PRiMeUM: a model for predicting risk of metastasis in uveal melanoma. Invest Ophthalmol Vis Sci. 2017;58(10):4096–105.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Walter SD, Chao DL, Feuer W, et al. Prognostic implications of tumor diameter in association with gene expression profile for uveal melanoma. JAMA Ophthalmol. 2016;134(7):734–40.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Correa ZM, Augsburger JJ. Independent prognostic significance of gene expression profile class and largest basal diameter of posterior uveal melanomas. Am J Ophthalmol. 2016;162:20–7. e1.

    Article  PubMed  Google Scholar 

  70. Demirci H, Niziol LM, Ozkurt Z, et al. Do largest basal tumor diameter and the American joint commission cancer staging influence prognostication by gene expression profiling in choroidal melanoma? Am J Ophthalmol. 2018;195:83–92.

    Google Scholar 

  71. Cook SA, Damato B, Marshall E, et al. Psychological aspects of cytogenetic testing of uveal melanoma: preliminary findings and directions for future research. Eye. 2008;23(3):581–5.

    Article  PubMed  Google Scholar 

  72. Schuermeyer I, Maican A, Sharp R, et al. Depression, anxiety, and regret before and after testing to estimate uveal melanoma prognosis. JAMA Ophthalmol. 2016;134(1):51–6.

    Article  PubMed  Google Scholar 

  73. Singh AD. Prognostication of uveal melanoma: a work in progress. JAMA Ophthalmol. 2016;134(7):740–1.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, Merseyside, UK

    Sarah E. Coupland, Helen Kalirai & Sophie Thornton

  2. Department of Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Liverpool, UK

    Azzam Taktak & Antonio Eleuteri

  3. Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK

    Bertil E. Damato

Authors
  1. Sarah E. Coupland
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  2. Azzam Taktak
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  3. Antonio Eleuteri
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  4. Helen Kalirai
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  5. Sophie Thornton
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  6. Bertil E. Damato
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Corresponding author

Correspondence to Sarah E. Coupland .

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Editors and Affiliations

  1. University of Oxford, Oxford, UK

    Bertil E. Damato

  2. Cole Eye Institute Cleveland Clinic, Cleveland, OH, USA

    Arun D. Singh

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Coupland, S.E., Taktak, A., Eleuteri, A., Kalirai, H., Thornton, S., Damato, B.E. (2019). Uveal Melanoma: Prognostication Methods. In: Damato, B., Singh, A. (eds) Clinical Ophthalmic Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-17879-6_19

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  • DOI: https://doi.org/10.1007/978-3-030-17879-6_19

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