Skip to main content
SpringerLink
Log in

Neue molekularpathologische Ansätze bei malignen Iristumoren

New molecular pathological strategies for malignant iris tumors

  • Leitthema
  • Published:
Der Ophthalmologe Aims and scope Submit manuscript

Zusammenfassung

Hintergrund

Die molekularpathologische Forschung bietet neue Chancen für das diagnostische und therapeutische Management von malignen Iristumoren. Neben der einfachen Immunhistologie und Polymerasekettenreaktionsanalyse können weitere Untersuchungsformen wie die multiplexe ligationsabhängige Sondenamplifikation, die Mikrosatellitenanalyse oder das Next-Generation-Sequencing verschiedene Mutationen im Tumorgenom detektieren.

Fragestellung

Es erfolgt die Darstellung aktueller molekularpathologischer Ansätze bei malignen Iristumoren.

Methoden

Dieser Beitrag bietet eine Übersicht über die aktuelle Literatur, basierend auf einer PubMed-Recherche und der klinischen Erfahrung bei Iristumoren.

Ergebnisse

Exemplarisch werden für das Irismelanom, das Irislymphom und die Iriskarzinommetastase diagnostische Besonderheiten und zielgerichtete Behandlungsoptionen dargestellt. Beim Irismelanom scheinen insbesondere Mutationen im GNA11- oder GNAQ-Gen (in ca. 85 % der Fälle) von Bedeutung zu sein. Ebenso empfiehlt es sich, den Monosomie-3-Status bei diesen Patienten zu untersuchen. Beim Irislymphom ist die molekularpathologische Aufarbeitung vor der exakten Diagnosestellung elementar. Ebenso ist die Detektion von Mutationen auf MYD88, BRAF, KLF2, ID3, TCF3, STAT3, RHo, TET2, IDH2, CXCR4, CD79B und DNMT3A hilfreich. Insbesondere der Nachweis des CD20-Antigens zieht eine therapeutische Relevanz nach sich, da diese Lymphome gut auf Rituximab, eine CD20-Antikörpertherapie, ansprechen. Auch bei Iriskarzinommetastasen sind Untersuchungen auf Mutationen hilfreich, da dann eine zielgerichtete Therapie möglich erscheint.

Schlussfolgerung

Die Molekularpathologie wird auch bei Iristumoren künftig unerlässlich werden, da sie den Schlüssel zu einer personalisierten Therapie darstellt.

Abstract

Background

Molecular pathological research offers new chances for the diagnostic and therapeutic management of malignant iris tumors. Besides immunohistological and polymerase chain reaction analyses further techniques, such as multiplex ligation-dependent probe amplification, microsatellite analyses and next-generation sequencing are able to detect various mutations in the tumor genome.

Objective

An up to date review of new molecular pathological strategies for malignant iris tumors was carried out.

Methods

This article provides a review of the recent literature based on a PubMed search and clinical experience with iris tumors.

Results

The diagnostic characteristics and targeted treatment options are presented, exemplified by iris melanoma and iris carcinoma metastases. In iris melanomas, mutations in the GNA11 and GNAQ genes (in approximately 85% of the cases) seem to be important. Furthermore, the monosomy-3 status should be investigated in these tumors. In iris lymphomas, molecular pathological analyses are essential for an exact diagnosis. Detection of mutations in MYD88, BRAF, KLF2, ID3, TCF3, STAT3, RHo, TET2, IDH2, CXCR4, CD79B and DNMT3A are helpful. In particular, the detection of the CD20 antigen is of therapeutic relevance because this lymphoma subgroup responds well to rituximab, a CD20 antibody treatment. In iris carcinoma metastases, investigations for mutations are helpful because then a targeted treatment seems to be possible.

Conclusion

Molecular pathological analyses will become essential in the future management of iris tumors because they play a key role towards a personalized treatment approach.

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

Abb. 1
Abb. 2

Literatur

  1. Chronopoulos A et al (2014) Small incision iris tumour biopsy using a cavernous sampling forceps. Br J Ophthalmol 98(11):1539–1542

    Article  PubMed  Google Scholar 

  2. Gokhale R et al (2015) Diagnostic fine-needle aspiration biopsy for Iris melanoma. Asia Pac J Ophthalmol (Phila) 4(2):89–91

    Article  Google Scholar 

  3. Chong CF et al (2014) Conservative biopsy excision and management of a large iris melanoma. Clin Exp Optom 97(3):278–279

    Article  PubMed  Google Scholar 

  4. Heindl LM et al (2017) Block excision of iridociliary tumors enables molecular profiling and immune vaccination. Ophthalmology 124(2):268–270

    Article  PubMed  Google Scholar 

  5. Mor JM, Koch KR, Heindl LM (2017) Diagnosis and therapy of Iris lesions. Klin Monbl Augenheilkd 234(12):1541–1554

    Article  PubMed  Google Scholar 

  6. Petousis V, Finger PT, Milman T (2011) Anterior segment tumor biopsy using an aspiration cutter technique: clinical experience. Am J Ophthalmol 152(5):771–775e1

    Article  PubMed  Google Scholar 

  7. Osterlind A (1987) Trends in incidence of ocular malignant melanoma in Denmark 1943–1982. Int J Cancer 40(2):161–164

    Article  CAS  PubMed  Google Scholar 

  8. McLaughlin CC et al (2005) Incidence of noncutaneous melanomas in the U.S. Cancer 103(5):1000–1007

    Article  PubMed  Google Scholar 

  9. Singh AD, Topham A (2003) Incidence of uveal melanoma in the United States: 1973–1997. Ophthalmology 110(5):956–961

    Article  PubMed  Google Scholar 

  10. Singh AD, Turell ME, Topham AK (2011) Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 118(9):1881–1885

    Article  PubMed  Google Scholar 

  11. Hu DN et al (2005) Population-based incidence of uveal melanoma in various races and ethnic groups. Am J Ophthalmol 140(4):612–617

    Article  PubMed  Google Scholar 

  12. Vajdic CM et al (2003) Incidence of ocular melanoma in Australia from 1990 to 1998. Int J Cancer 105(1):117–122

    Article  CAS  PubMed  Google Scholar 

  13. Damato BE, Coupland SE (2012) Differences in uveal melanomas between men and women from the British Isles. Eye (Lond) 26(2):292–299

    Article  CAS  Google Scholar 

  14. Shields CL et al (2012) Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases. Retina 32(7):1363–1372

    Article  PubMed  Google Scholar 

  15. Shields CL et al (2013) Iris nevus growth into melanoma: analysis of 1611 consecutive eyes: the ABCDEF guide. Ophthalmology 120(4):766–772

    Article  PubMed  Google Scholar 

  16. Shields CL et al (2001) Iris melanoma: risk factors for metastasis in 169 consecutive patients. Ophthalmology 108(1):172–178

    Article  CAS  PubMed  Google Scholar 

  17. Khan S et al (2012) Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study. Arch Ophthalmol 130(1):57–64

    Article  PubMed  Google Scholar 

  18. Damato B (2012) Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye (Lond) 26(9):1157–1172

    Article  CAS  Google Scholar 

  19. Grossniklaus HE et al (1995) Histopathology, morphometry, and nuclear DNA content of iris melanocytic lesions. Invest Ophthalmol Vis Sci 36(3):745–750

    CAS  PubMed  Google Scholar 

  20. Sisley K et al (1998) Cytogenetics of iris melanomas: disparity with other uveal tract melanomas. Cancer Genet Cytogenet 101(2):128–133

    Article  CAS  PubMed  Google Scholar 

  21. Shields CL et al (2009) Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol 127(8):989–998

    Article  PubMed  Google Scholar 

  22. Shields CL et al (2011) Cytogenetic testing of iris melanoma using fine needle aspiration biopsy in 17 patients. Retina 31(3):574–580

    Article  PubMed  Google Scholar 

  23. Mensink HW et al (2011) Chromosomal aberrations in iris melanomas. Br J Ophthalmol 95(3):424–428

    Article  CAS  PubMed  Google Scholar 

  24. Harbour JW et al (2013) Gene expressing profiling of iris melanomas. Ophthalmology 120(1):213e1–213e3

    Article  Google Scholar 

  25. Prescher G, Bornfeld N, Becher R (1994) Two subclones in a case of uveal melanoma. Relevance of monosomy 3 and multiplication of chromosome 8q. Cancer Genet Cytogenet 77(2):144–146

    Article  CAS  PubMed  Google Scholar 

  26. Prescher G et al (1996) Prognostic implications of monosomy 3 in uveal melanoma. Lancet 347(9010):1222–1225

    Article  CAS  PubMed  Google Scholar 

  27. White VA, Horsman DE, Rootman J (1995) Cytogenetic characterization of an iris melanoma. Cancer Genet Cytogenet 82(1):85–87

    Article  CAS  PubMed  Google Scholar 

  28. Krishna Y et al (2016) Genetic findings in treatment-naive and proton-beam-radiated iris melanomas. Br J Ophthalmol 100(7):1012–1016

    Article  PubMed  Google Scholar 

  29. Scholz SL et al (2017) Frequent GNAQ, GNA11, and EIF1AX mutations in Iris melanoma. Invest Ophthalmol Vis Sci 58(9):3464–3470

    Article  CAS  PubMed  Google Scholar 

  30. van Poppelen NM et al (2018) Genetic background of iris melanomas and iris melanocytic tumors of uncertain malignant potential. Ophthalmology 125(6):904–912

    Article  PubMed  Google Scholar 

  31. Scholz SL et al (2018) Re: van Poppelen et al.: Genetic background of iris melanomas and iris melanocytic tumors of uncertain malignant potential (Ophthalmology. 2018;125:904–912). Ophthalmology 125(11):e78–e79

    Article  PubMed  Google Scholar 

  32. Wallander ML et al (2011) KIT mutations in ocular melanoma: frequency and anatomic distribution. Mod Pathol 24(8):1031–1035

    Article  CAS  PubMed  Google Scholar 

  33. Shoushtari AN, Carvajal RD (2014) GNAQ and GNA11 mutations in uveal melanoma. Melanoma Res 24(6):525–534

    Article  CAS  PubMed  Google Scholar 

  34. Metz CH et al (2013) Uveal melanoma: current insights into clinical relevance of genetic testing. Klin Monbl Augenheilkd 230(7):686–691

    Article  CAS  PubMed  Google Scholar 

  35. Henriquez F et al (2007) The T1799A BRAF mutation is present in iris melanoma. Invest Ophthalmol Vis Sci 48(11):4897–4900

    Article  PubMed  Google Scholar 

  36. Karydis I et al (2016) Clinical activity and safety of pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma. Oncoimmunology 5(5):e1143997

    Article  PubMed  PubMed Central  Google Scholar 

  37. Schuler-Thurner B et al (2015) Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma. Ophthalmologe 112(12):1017–1021

    Article  CAS  PubMed  Google Scholar 

  38. Kakkassery V, Wunderlich MI (2016) Ocular lymphomas. Klin Monbl Augenheilkd 233(10):1175–1191

    Article  PubMed  Google Scholar 

  39. Coupland SE, Damato B (2006) Lymphomas involving the eye and the ocular adnexa. Curr Opin Ophthalmol 17:523–531

    PubMed  Google Scholar 

  40. Coupland SE (2013) Molecular pathology of lymphoma. Eye (Lond) 27(2):180–189

    Article  CAS  Google Scholar 

  41. Coupland SE, Damato B (2006) Lymphomas involving the eye and the ocular adnexa. Curr Opin Ophthalmol 17(6):523–531

    PubMed  Google Scholar 

  42. Rosenquist R et al (2016) Clinical impact of recurrently mutated genes on lymphoma diagnostics: state-of-the-art and beyond. Haematologica 101(9):1002–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Witkowska M, Smolewski P (2016) Development of anti-CD20 antigen-targeting therapies for B‑cell lymphoproliferative malignancies—the state of the art. Curr Drug Targets 17(9):1072–1082

    Article  CAS  PubMed  Google Scholar 

  44. Shields CL et al (2018) Uveal metastasis: clinical features and survival outcome of 2214 tumors in 1111 patients based on primary tumor origin. Middle East Afr J Ophthalmol 25(2):81–90

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wunderlich MI et al (2016) Unusual masquerade of an ocular carcinoma metastasis. Ophthalmologe 113(8):690–693

    Article  CAS  PubMed  Google Scholar 

  46. Flaherty KT et al (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 367(18):1694–1703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Petrelli F et al (2012) Relationship between skin rash and outcome in non-small-cell lung cancer patients treated with anti-EGFR tyrosine kinase inhibitors: a literature-based meta-analysis of 24 trials. Lung Cancer 78(1):8–15

    Article  PubMed  Google Scholar 

  48. Petrelli F et al (2012) Biological agents alone or in combination as second-line therapy in advanced non-small-cell lung cancer: systematic review of randomized studies. Expert Rev Anticancer Ther 12(10):1299–1312

    Article  CAS  PubMed  Google Scholar 

  49. Cai J et al (2013) Correlation of bevacizumab-induced hypertension and outcomes of metastatic colorectal cancer patients treated with bevacizumab: a systematic review and meta-analysis. World J Surg Oncol 11:306

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Augenheilkunde, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    V. Kakkassery & S. Grisanti

  2. Klinik und Poliklinik für Augenheilkunde, Universitätsmedizin Rostock, Rostock, Deutschland

    A. M. Jünemann & B. O. Scheef

  3. Zentrum für Augenheilkunde, Universitätsklinikum zu Köln, Köln, Deutschland

    L. M. Heindl

  4. Centrum für Integrierte Onkologie (CIO) Köln-Bonn, Köln-Bonn, Deutschland

    L. M. Heindl

Authors
  1. V. Kakkassery
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. M. Jünemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. O. Scheef
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Grisanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. M. Heindl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Kakkassery.

Ethics declarations

Interessenkonflikt

V. Kakkassery, A.M. Jünemann, B.O. Scheef, S. Grisanti und L.M. Heindl geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren. Alle Patienten, die über Bildmaterial oder anderweitige Angaben innerhalb des Manuskripts zu identifizieren sind, haben hierzu ihre schriftliche Einwilligung gegeben. Im Falle von nicht mündigen Patienten liegt die Einwilligung eines Erziehungsberechtigten oder des gesetzlich bestellten Betreuers vor.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kakkassery, V., Jünemann, A.M., Scheef, B.O. et al. Neue molekularpathologische Ansätze bei malignen Iristumoren. Ophthalmologe 116, 324–331 (2019). https://doi.org/10.1007/s00347-018-0840-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00347-018-0840-8

Schlüsselwörter

Keywords

Search

Navigation