Skip to main content
SpringerLink
Log in

Genetic analysis of uveal melanoma by array comparative genomic hybridization before and after radiotherapy

  • original article
  • Published:
Spektrum der Augenheilkunde Aims and scope Submit manuscript

Summary

Background

Genetic analysis of choroidal melanoma is frequently used to estimate the risk of metastatic spread of the tumor. Obtaining a biopsy for genetic analysis, however, can be difficult and sometimes unsuccessful. We evaluated the feasibility and accuracy of genetic testing using array comparative genomic hybridization (CGH) after radiotherapy, from tumor samples obtained by endoresection or after secondary enucleation.

Material and methods

Fifteen choroidal melanoma samples obtained after radiotherapy (Ruthenium-106 plaque brachytherapy or Gamma-Knife radiosurgery) were analyzed by array CGH to detect chromosomal aberrations (monosomy 3 and trisomy 8q), and the results were compared with pre-irradiation findings in five cases.

Results

Array CGH was successfully performed in all 15 cases. Time from radiotherapy to obtaining the sample for cytogenetic testing was between 14 and 879 days. Results of post-radiotherapy genetic analysis did not differ from pre-radiotherapy findings.

Conclusion

Post-radiation CGH appears to be a promising option for prognostic testing if a first biopsy before radiotherapy failed or was not performed. It could be useful to avoid an additional surgical procedure before radiotherapy if vitrectomy or endoresection is planned after radiotherapy.

Zusammenfassung

Hintergrund

Die genetische Untersuchung von Aderhautmelanomen ist eine zunehmend häufiger eingesetzte Methode, um das Risiko der Metastasenentwicklung bei PatientInnen mit Aderhautmelanomen einzuschätzen. Die Gewinnung einer Gewebeprobe zur Durchführung der Untersuchung ist jedoch manchmal schwierig und nicht in allen Fällen erfolgreich. Wir untersuchten die Durchführbarkeit und Genauigkeit der genetischen Untersuchung von Aderhautmelanomen mittels array comparative genomic hybridization (CGH) nach Strahlentherapie, an mittels Endoresektion oder nach Enukleation gewonnenem Tumormaterial.

Material und Methode

Fünfzehn Gewebeproben von strahlentherapeutisch behandelten Aderhautmelanomen wurden mittels array-CGH auf Veränderungen an den Chromosomen 3 und 8 untersucht (Monosomie 3, Trisomie 8q). Die Ergebnisse wurden mit den in fünf Fällen vorliegenden Resultaten der genetischen Untersuchung vor Bestrahlung verglichen.

Resultate

Die array CGH konnte in allen 15 Fällen nach Bestrahlung erfolgreich durchgeführt werden. Die Zeitspanne von der Bestrahlung bis zur genetischen Untersuchung lag zwischen 14 und 879 Tagen. Die Resultate der genetischen Untersuchung nach Bestrahlung unterschieden sich nicht von den Ergebnissen der in 5 Fällen vorliegenden Ergebnissen vor der Bestrahlung.

Schlußfolgerung

Die array CGH von Aderhautmelanomen nach Strahlentherapie erscheint eine vielversprechende Option zur prognostischen Unteruchung in den Fällen zu sein, in denen eine Biopsie vor Bestrahlung nicht durchgeführt wurde oder nicht erfolgreich war. Im Falle einer geplanten Endoresektion nach Bestrahlung, könnte auf einen zusätzlichen Eingiff zu Biopsie vor der Bestrahlung verzichtet werden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Singh AD, Topham A. Incidence of uveal melanoma in the United States: 1973–1997. Ophthalmology. 2003;110:956–61.

    Article  PubMed  Google Scholar 

  2. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma. a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83:1664–78.

    Article  Google Scholar 

  3. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118:1881–5.

    Article  PubMed  Google Scholar 

  4. Singh AD, Topham A. Survival rates with uveal melanoma in the United States: 1973–1997. Ophthalmology. 2003;110:962–5.

    Article  PubMed  Google Scholar 

  5. Mudhar HS, Parsons MA, Sisley K, et al. A critical appraisal of the prognostic and predictive factors for uveal malignant melanoma. Histopathology. 2004;45:1–12.

    Article  PubMed  CAS  Google Scholar 

  6. Prescher G, Bornfeld N, Becher R. Nonrandom chromosomal abnormalities in primary uveal melanoma. J Natl Cancer Inst. 1990;82:1765–9.

    Article  PubMed  CAS  Google Scholar 

  7. Sisley K, Rennie IG, Cottam DW, et al. Cytogenetic findings in six posterior uveal melanomas: involvement of chromosomes 3, 6, and 8. Genes, chromosomes & cancer. 1990;2:205–9.

    Article  CAS  Google Scholar 

  8. Prescher G, Bornfeld N, Hirche H, et al. Prognostic implications of monosomy 3 in uveal melanoma. Lancet. 1996;347:1222–5.

    Article  PubMed  CAS  Google Scholar 

  9. Sisley K, Rennie IG, Parsons MA, et al. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes, chromosomes & cancer. 1997;19:22–8.

    Article  CAS  Google Scholar 

  10. Damato B, Coupland SE. Translating uveal melanoma cytogenetics into clinical care. Arch Ophthalmol. 2009;127:423–9.

    Article  PubMed  Google Scholar 

  11. Damato B, Duke C, Coupland SE, et al. Cytogenetics of uveal melanoma: a 7-year clinical experience. Ophthalmology. 2007;114:1925–31.

    Article  PubMed  Google Scholar 

  12. Midena E, Bonaldi L, Parrozzani R et al In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy. European journal of ophthalmology. 2006;16:422–5.

    PubMed  CAS  Google Scholar 

  13. Young TA, Burgess BL, Rao NP, et al. Transscleral fine-needle aspiration biopsy of macular choroidal melanoma. Am J Ophthalmol. 2008;145:297–302.

    Article  PubMed  Google Scholar 

  14. Wackernagel W, Schmutzer M, Mayer CF, et al. Biopsy of intraocular tumors in clinically uncertain diagnosis. Spektrum der Augenheilkunde. 2005;19:171–5.

    Article  Google Scholar 

  15. Bechrakis NE, Foerster MH. Neoadjuvant proton beam radiotherapy combined with subsequent endoresection of choroidal melanomas. Int Ophthalmol Clin. 2006;46:95–107.

    Article  PubMed  Google Scholar 

  16. Singh AD, Triozzi PL. Endoresection for choroidal melanoma: palliative or curative intent? Br J Ophthalmol. 2008;92:1015–6.

    Article  PubMed  CAS  Google Scholar 

  17. Bechrakis NE, Blatsios G, Schmid E, et al. Surgical resection techniques of large uveal melanomas. Spektrum Der Augenheilkunde. 2010;24:17–22.

    Article  Google Scholar 

  18. Herwig M, Eter N. 23-gauge versus 20-gauge vitrectomy: analysis of 110 consecutive cases undergoing epiretinal membrane peeling and macular hole repair. Spektrum Der Augenheilkunde. 2012;26:172–4.

    Article  Google Scholar 

  19. Bezatis A, Laufenbock C, Zehetner C, Kieselbach G, Kralinger M, et al. Macular hole surgery: anatomical and functional results. Spektrum Der Augenheilkunde. 2011;25:302–5.

    Article  Google Scholar 

  20. Tarmann L, Wedrich A, Hass A, et al. Limited vitrectomy with intravitreal bevacizumab, rt-PA and gas for submacular hemorrhage due to age-related macular degeneration. Spektrum Der Augenheilkunde. 2012;26:197–201.

    Article  Google Scholar 

  21. Mayer CF, Langmann G, Wackernagel W, et al. Globe preservation and visual function after endoresection and Gamma-Knife radiosurgery for uveal melanomas. Spektrum der Augenheilkunde. 2009;23:347–52.

    Article  Google Scholar 

  22. Shields CL, Ganguly A, Materin MA, et al. Chromosome 3 analysis of uveal melanoma using fine-needle aspiration biopsy at the time of plaque radiotherapy in 140 consecutive cases. Transactions of the American Ophthalmological Society. 2007;105:43–52; discussion–3.

    PubMed  Google Scholar 

  23. Young TA, Rao NP, Glasgow BJ, et al. Fluorescent in situ hybridization for monosomy 3 via 30-gauge fine-needle aspiration biopsy of choroidal melanoma in vivo. Ophthalmology. 2007;114:142–6.

    Article  PubMed  Google Scholar 

  24. Foster WJ, Harbour JW, Holekamp NM, et al. Pars plana vitrectomy in eyes containing a treated posterior uveal melanoma. Am J Ophthalmol. 2003;136:471–6.

    Article  PubMed  Google Scholar 

  25. Glasgow BJ, Brown HH, Zargoza AM, et al. Quantitation of tumor seeding from fine needle aspiration of ocular melanomas. Am J Ophthalmol. 1988;105:538–46.

    PubMed  CAS  Google Scholar 

  26. Suesskind D, Ulmer A, Schiebel U, et al. Circulating melanoma cells in peripheral blood of patients with uveal melanoma before and after different therapies and association with prognostic parameters: a pilot study. Acta ophthalmologica. 2011;89:17–24.

    Google Scholar 

  27. Garcia-Arumi J, Zapata MA, Balaguer O, et al. Endoresection in high posterior choroidal melanomas: long-term outcome. Br J Ophthalmol. 2008;92:1040–5.

    Article  PubMed  CAS  Google Scholar 

  28. Schefler AC, Gologorsky D, Marr BP et al Extraocular extension of uveal melanoma after fine-needle aspiration, vitrectomy, and open biopsy. JAMA ophthalmology. 2013;131:1220–4.

    Google Scholar 

  29. Pe’er J, Stefani FH, Seregard S, et al. Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study. Br J Ophthalmol. 2001;85:1208–12.

    Article  PubMed  Google Scholar 

  30. Tschentscher F, Husing J, Holter T et al Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer research. 2003;63:2578–84.

    Google Scholar 

  31. Onken MD, Worley LA, Ehlers JP et al Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer research. 2004;64:7205–9.

    Google Scholar 

Download references

Acknowledgments

We thank Anna Obenauf, PhD, from Department of Human Genetics, Medical University Graz, for the support in genetic analysis of the samples.

Conflict of interest

Werner Wackernagel, Lisa Tarmann, Christoph Mayer, Gerald Langmann, and Andreas Wedrich declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Medical University Graz, Auenbruggerplatz 4, 8036, Graz, Austria

    Werner Wackernagel,  Lisa Tarmann,  Christoph Mayer,  Gerald Langmann &  Andreas Wedrich

Authors
  1. Werner Wackernagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa Tarmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christoph Mayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gerald Langmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreas Wedrich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Werner Wackernagel.

Additional information

Data were presented in part at the 51st meeting of the Austrian Ophthalmological Society, ARVO Science Day, May 14th, 2010, Zell am See, Austria.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wackernagel, W., Tarmann, L., Mayer, C. et al. Genetic analysis of uveal melanoma by array comparative genomic hybridization before and after radiotherapy. Spektrum Augenheilkd. 27, 286–291 (2013). https://doi.org/10.1007/s00717-013-0195-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00717-013-0195-0

Keywords

Search

Navigation