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In vivo monosomy 3 detection of posterior uveal melanoma: 3-year follow-up

  • Oncology
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Abstract

Background

Monosomy 3 is a highly specific marker for poor prognosis in posterior uveal melanoma. Unfortunately, cytogenetic prognostication is limited to enucleated eyes or resected tumors. The aim of this study was to evaluate mid-term natural history and safety of in vivo detection of chromosome 3 status in posterior uveal melanomas undergoing plaque brachytherapy.

Methods

A 25-gauge transscleral fine needle aspiration biopsy (FNAB) was performed in 32 eyes affected by posterior uveal melanoma undergoing plaque brachytherapy, just before applying the radioactive plaque. Sampled material underwent fluorescence in situ hybridization (FISH) with centromeric probes for chromosome 3. All patients had a follow-up of at least 36 months.

Results

Mean follow-up was 47.1 ± 8.5 months. Mean largest basal diameter and mean thickness of the tumors were 12.5 ± 2.7 mm and 8 ± 2.3 mm respectively. FNAB yielded sufficient material in 26 of 32 cases (81.2%). Adequacy of the sample ranged from 91.1% (ciliary body tumors) to 76.8% (choroidal tumors). Seventeen cases had monosomy 3 (65.3%). No correlation was found between monosomy 3 and tumor dimensions or location (ciliary body vs choroidal tumors). No early and mid-term local complications were documented. Seven patients (21.8%) died during follow-up: five (15.6%) of them died due to metastatic disease (all had monosomy 3 tumors).

Conclusions

Posterior uveal melanomas may be adequately and safely sampled, by intra-operative transscleral FNAB, to detect in vivo monosomy 3.

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References

  1. Seregard S (1996) Posterior uveal melanoma. Acta Ophthalmol Scand 74:315–329

    Article  PubMed  CAS  Google Scholar 

  2. Naus NC, Verhoeven ACA, van Drunen E, Slater R, Mooy CM, Paridaens DA, Luyten GP, de Klein A (2002) Detection of genetic prognostic markers in uveal melanoma biopsy using fluorescence in situ hybridization. Clin Cancer Res 8:534–539

    PubMed  Google Scholar 

  3. Gamel JW, McLean IW, McCurdy JB (1993) Biologic distinctions between cure and time to death in 2892 patients with intraocular melanoma. Cancer 119:786–791

    Google Scholar 

  4. Kujala E, Kivela T (2005) Tumor, node, metastasis classification of malignant ciliary body and choroidal melanoma evaluation of the 6th edition and future directions. Ophthalmology 112:1135–1144

    Article  PubMed  Google Scholar 

  5. Schmittel A, Bechrakis NE, Martus P, Mutlu D, Sheibenbogen C, Bornfeld N, Foerster MH, Thiel E, Keilholz U (2004) Independent prognostic factors for distant metastases and survival in patients with primary uveal melanoma. Eur J Cancer 40:2389–2395

    Article  PubMed  Google Scholar 

  6. Gambrelle J, Labialle S, Dayan G, Gayet L, Barakat S, Grange JD, Baggetto LG (2004) Toward monosomy 3 as the main prognosis factor of uveal melanoma: current cytogenetic data. J Fr Ophtalmol 27:1061–1067

    Article  PubMed  CAS  Google Scholar 

  7. Kilic E, Naus NC, van Gils W, Claver CC, van Til ME, Verbiest MM, Stijnen T, Mooy CM, Paridaens D, Beverloo HB, Luyten GP, de Klein A (2005) Concurrent loss of chromosome arm 1p and chromosome 3 predicts a decreased disease-free survival in uveal melanoma patients. Invest Ophthalmol Vis Sci 46:2253–2257

    Article  PubMed  Google Scholar 

  8. Scholes AGM, Damato BE, Nunn J, Hiscott P, Grierson I, Field JK (2003) Monosomy 3 in uveal melanoma: correlation with clinical and histologic predictors of survival. Invest Ophthalmol Vis Sci 44:1008–1011

    Article  PubMed  Google Scholar 

  9. Höglund M, Gisselsson D, Hansen GB, White VA, Sall T, Mitelman F, Horsman D (2004) Dissecting karyotypic patterns in malignant melanomas: Temporal clustering of losses and gains in melanoma karyotypic evolution. Int J Cancer 108:57–65

    Article  PubMed  CAS  Google Scholar 

  10. Sisley K, Rennie IG, Cottam DW, Potter AM, Potter CW, Rees RC (1990) Cytogenetic findings in six posterior uveal melanomas: involvement of chromosomes 3, 6 and 8. Genes Chromosomes Cancer 2:205–209

    Article  PubMed  CAS  Google Scholar 

  11. Sandinha M, Farquharson M, Mckay I, Roberts F (2005) Monosomy 3 predicts death but not time to death in choroidal melanoma. Invest Ophthalmol Vis Sci 46:1497–1501

    Article  Google Scholar 

  12. Onken M, Worley L, Ehlers J, Arbour JW (2004) Genes expression profiling reveals two molecular classes and predict metastatic death. Cancer Res 64:7205–7209

    Article  PubMed  CAS  Google Scholar 

  13. Prescher G, Bornfeld N, Becher R (1990) Non-random chromosomal abnormalities in primary uveal melanoma. J Natl Cancer Inst 82:1765–1769

    Article  PubMed  CAS  Google Scholar 

  14. Sisley K, Cottam DW, Rennie IG, Parson MA, Potter AM, Potter CW, Rees RC (1992) Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma. Genes Chromosomes Cancer 5:197–200

    Article  PubMed  CAS  Google Scholar 

  15. Sisley K, Tattersall N, Dyson M, Smith K, Mudhar H, Rennie I (2006) Multiplex fluorescence in situ hybridization identifies novel rearrangements of chromosome 6, 15, and 18 in primary uveal melanoma. Exp Eye Res 83:554–559

    Article  PubMed  CAS  Google Scholar 

  16. Tschentscher F, Hüsing J, Hölter T, Kruse E, Dresen IG, Jockel KH, Anastassiou G, Schilling H, Bornfeld N, Horsthemke B, Lohmann DR, Zeschnigk M (2003) Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer Res 63:2578–2584

    PubMed  CAS  Google Scholar 

  17. Sisley K, Nichols C, Parsons MA, Farr R, Rees RC, Rennie IG (1998) Clinical applications of chromosome analysis, from fine needle aspiration biopsies, of posterior uveal melanomas. Eye 12:203–207

    PubMed  Google Scholar 

  18. Midena E, Bonaldi L, Parrozzani R, Tebaldi E, Boccassini B, Vujosevic S (2006) In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy. Euro J Ophthalmol 16:422–425

    CAS  Google Scholar 

  19. Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel KH, Becher R (1996) Prognostic implications of monosomy 3 in uveal melanoma. Lancet 347:1222–1225

    Article  PubMed  CAS  Google Scholar 

  20. Kvanta A, Seregard S, Kopp ED, All-Ericsson C, Landau I, Berglin L (2005) Choroidal Biopsies for intraocular tumors of indeterminate origin. Am J Ophthalmology 140:1002–1006

    Article  Google Scholar 

  21. Shields JA, Shields CL, Ehya H, Eagle RCJ, De Potter P (1993) Fine-needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology 100:1677–1684

    PubMed  CAS  Google Scholar 

  22. Caminal JM, Sanz S, Carreras M, Català I, Arruga J, Rocca G (2006) Epibulbar seeding at the site of a transvitreal fine-needle aspiration biopsy. Arch Ophthalmology 124:587–589

    Article  Google Scholar 

  23. Shields CL, Ganguly A, Materin MA, Teixeira L, Mashayekhi A, Swanson LA, Marr BP, Shields JA (2007) Chromosome 3 analysis of uveal melanoma using fine-needle aspiration biopsy at the time of plaque radiotherapy in 140 consecutive cases. Arch Ophthalmol 125:1017–1024

    Article  PubMed  Google Scholar 

  24. Sen J, Groenewald C, Hiscott P, Smith P, Damato B (2006) Transretinal choroidal tumor biopsy with a 25-gauge vitrector. Ophthalmology 113:1028–1031

    Article  PubMed  Google Scholar 

  25. Sandinha T, Farquharson M, McKay I, Roberts F (2006) Correlation of Hetergeneity for chromosome 3 copy number with cell type in choroidal melanoma of Mixed-cell type. Invest Ophthalmol Vis Sci 47:5177–5180

    Article  PubMed  Google Scholar 

  26. Maat W, Jordanova ES, van Zelderen-Bhola SL, Barthen ER, Wessels HW, Schalij-Delfos NE, Jager MJ (2007) The heterogeneous distribution of monosomy 3 in uveal melanomas: implications for prognostication based on fine-needle aspiration biopsies. Arch Pathol Lab Med 131:91–96

    PubMed  Google Scholar 

  27. Meir T, Zeschnigk M, Masshofer L, Pe’er J, Chowers I (2007) The spatial distribution of monosomy 3 and network vasculogenic mimicry patterns in uveal melanoma. Invest Ophthalmol Vis Sci 48:1918–1922

    Article  PubMed  Google Scholar 

  28. Onken MD, Worley LA, Parson E, Char HD, Bowcock AM, Harbour JW (2007) Prognostic testing in uveal melanoma by trancriptomic profiling of fine needle biopsy specimens. Clin Cancer Res 13:2923–2927

    Article  PubMed  CAS  Google Scholar 

  29. Worley LA, Onken MD, Parson E, Robirds D, Branson J, Char DH, Perry A, Harbour JW (2007) Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma. Clin Canc Res 13:1466–1471

    Article  CAS  Google Scholar 

  30. Sisley K, Rennie IG, Parsons MA, Jacques R, Hammond DW, Bell SM, Potter AM, Rees RC (1997) Abnormalities of chromosomes 3 and 8, in posterior uveal melanoma, correlate with prognosis. Genes Chromosom Cancer 19:22–28

    Article  PubMed  CAS  Google Scholar 

  31. Collaborative Ocular Melanoma Study Group (2001) Report No. 26. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma. Arch Ophthalmol 119:961–965

    Google Scholar 

  32. Aalto Y, Eriksson L, Seregard S, Larsson O, Knuutila S (2001) 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 42:313–317

    PubMed  CAS  Google Scholar 

  33. Hughes S, Damato BE, Giddings I, Hiscott PS, Humphreys J, Houlston RS (2005) Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3. Br J Cancer 93:1191–1196

    Article  PubMed  CAS  Google Scholar 

  34. Tschentscher F, Prescher G, Zeschnigk M, Horsthemke B, Lohmann DT (2000) Identification of chromosome 3, 6, and 8 aberrations in uveal melanoma by microsatellite analysis in comparison to comparative genomic hybridization. Cancer Genet Cytogenet 122:13–17

    Article  PubMed  CAS  Google Scholar 

  35. Worley LA, Onken MD, Person E, Robirds D, Branson J, Char DH, Perry A, Harbour JW (2007) Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma. Clin Cancer Res 13:1466–1471

    Article  PubMed  CAS  Google Scholar 

  36. Onken MD, Worley LA, Person E, Char DH, Bowcock AM, Harbour JW (2007) 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 13:2923–2927

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, University of Padova, Via Giustiniani 2, 35128, Padova, Italy

    Edoardo Midena, Raffaele Parrozzani, Pietro P. Radin & Barbara Boccassini

  2. U.O.C Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto, IRCCS, Via Gattamelata 64, 35128, Padova, Italy

    Laura Bonaldi

  3. Fondazione GB Bietti per l’Oftalmologia, IRCCS, Via Livenza 3, 00198, Roma, Italy

    Edoardo Midena & Stela Vujosevic

Authors
  1. Edoardo Midena
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  2. Laura Bonaldi
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  3. Raffaele Parrozzani
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  4. Pietro P. Radin
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  6. Stela Vujosevic
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Correspondence to Edoardo Midena.

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The authors have no financial interest in the subject of this paper.

The authors have full control of all primary data and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data if requested.

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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 246, 609–614 (2008). https://doi.org/10.1007/s00417-007-0692-4

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  • DOI: https://doi.org/10.1007/s00417-007-0692-4

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