Skip to main content
SpringerLink
Log in

Das Merkel-Zell-Polyomavirus in der Pathogenese nichtmelanozytärer Hauttumoren

Merkel cell polyomavirus in the pathogenesis of non-melanoma skin cancer

  • Aktuelles aus der Forschung in der Pathologie
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Das Merkel-Zellkarzinom ist ein sehr aggressives neuroendokrines Karzinom der Haut. Das kürzlich in Merkel-Zellkarzinomen identifizierte Merkel-Zell-Polyomavirus (MCPyV) ist in der Mehrheit der Merkel-Zellkarzinome (>75%) nachzuweisen. MCPyV integriert klonal in die Tumor-DNA und weist tumorspezifische Punktmutationen im „Large-T-Antigen“ auf. Zur Fragestellung, ob MCPyV in der Pathogenese weiterer nichtmelanozytärer Hauttumoren eine Rolle spielt, haben wir Plattenepithelkarzinome, M. Bowen und Basalzellkarzinome immunsupprimierter und immunkompetenter Patienten auf die Anwesenheit von MCPyV einschließlich Mutationsstatus des „Large-T-Antigens“ getestet. Hierbei ließ sich MCPyV signifikant häufiger in den Hauttumoren der immunsupprimierten Patienten nachweisen (p<0,001). Tumorspezifische MCPyV-Mutationen im „Large-T-Antigen“ waren in dem vorliegenden Kollektiv nicht nachzuweisen. Die Anwesenheit von MCPyV in den Tumorzellen wurde mittels FISH-Analysen bestätigt. Obwohl MCPyV sich in den Tumorzellen der Plattenepithekarzinome, M. Bowen und Basalzellkarzinome der Haut nachweisen ließ, sind weitere Untersuchungen zur Rolle des MCPyV in der Pathogenese dieser Tumoren notwendig.

Abstract

Merkel cell carcinoma (MCC) is a very aggressive neuroendocrine carcinoma of the skin. The recently identified Merkel cell polyomavirus (MCPyV) is present in the majority of MCCs. MCPyV clonally integrates in the tumor DNA and tumor-specific viral mutations are detected within the large T-antigen. To elucidate a possible role of MCPyV in the pathogenesis of other non-melanoma skin cancers (NMSC), i.e. squamous cell carcinoma, Bowen’s disease and basal cell carcinoma we tested a group of these tumors in immunosuppressed and immunocompetent patients. In addition we tested MCPyV-positive tumors for viral mutations within the large T-antigen. MCPyV DNA was significantly more frequently detected in the NMSC of the immunosuppressed patients (p<0.001). No tumor specific mutations were found within the large T-antigen. The presence of the virus in tumor cells was confirmed by FISH analysis. Although MCPyV is present in the tumor cells of squamous cell carcinoma, Bowen’s disease and basal cell skin carcinoma, further investigations into the role of MCPyV in the pathogenesis of these tumors is needed.

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

Literatur

  1. Allander T, Andreasson K, Gupta S et al (2007) Identification of a third human polyomavirus. J Virol 81:4130–4136

    Article  CAS  PubMed  Google Scholar 

  2. Becker JC, Houben R, Ugurel S et al (2009) MC Polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol (doi:10.1038/jid.2008.198)

    Google Scholar 

  3. Dworkin AM, Tseng SY, Allain DC et al (2009) Merkel cell polyomavirus in cutaneous squamous cell carcinoma of immunocompetent individuals. J Invest Dermatol [Epub ahead of print]

  4. Feng H, Shuda M, Chang Y, Moore PS (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319:1096–1100

    Article  CAS  PubMed  Google Scholar 

  5. Gardner SD, Field AM, Coleman DV, Hulme B (1971) New human papovavirus (B.K.) isolated from the urine after renal transplantation. Lancet 1:1253–1257

    Article  CAS  PubMed  Google Scholar 

  6. Garneski KM, Warcola AH, Feng Q et al (2009) Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol (doi:10.1038/jid.2008.229?

    Google Scholar 

  7. Gaynor AM, Nissen MD, Whiley DM et al (2007) Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog 3:595–604

    Article  CAS  Google Scholar 

  8. Graffi A, Schramm T, Graffi I et al (1968) Virus-associated skin tumors of the Syrian hamster: preliminary note. J Natl Cancer Inst 40:867–873

    CAS  PubMed  Google Scholar 

  9. Gross L (1953) A filterable agent, recovered from Ak leukemic extracts, causing salivary gland carcinomas in C3H mice. Proc Soc Exp Biol Med 83:414–421

    CAS  PubMed  Google Scholar 

  10. Hampton T (2005) Skin cancer’s ranks rise: immunosuppression to blame. JAMA 294:1476–1480

    Article  CAS  PubMed  Google Scholar 

  11. Hilleman MR (1998) Discovery of simian virus 40 (SV40) and its relationship to poliomyelitis virus vaccines. Dev Biol Stand 94:183–190

    CAS  PubMed  Google Scholar 

  12. Ho WL, Murphy GM (2008) Update on the pathogenesis of post-transplant skin cancer in renal transplant recipients. Br J Dermatol 158:217–224

    Article  CAS  PubMed  Google Scholar 

  13. Hodgson NC (2005) Merkel cell carcinoma: changing incidence trends. J Surg Oncol 89:1–4

    Article  PubMed  Google Scholar 

  14. Jensen K, Kohler S, Rouse RV (2000) Cytokeratin staining in Merkel cell carcinoma: an immunohistochemical study of cytokeratins 5/6, 7, 17 and 20. Appl Immunohistochem Mol Morphol 8:310–315

    Article  CAS  PubMed  Google Scholar 

  15. Kassem A, Schöpflin A, Diaz C et al (2008) Frequent detection of Merkel cell polyoma-virus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res 68:5009–5013

    Article  CAS  PubMed  Google Scholar 

  16. Kassem A, Technau K, Kurz AK et al (2009) Merkel cell polyomavirus sequences are frequently detected in nonmelanoma skin cancer of immunosuppressed patients. Int J Cancer 125:356–361

    Article  CAS  PubMed  Google Scholar 

  17. Lemos B, Nghiem P (2007) Merkel cell carcinoma: more deaths but still no pathway to blame. J Invest Dermatol 127:2100–2103

    Article  CAS  PubMed  Google Scholar 

  18. Padgett BL, Walker DL, ZuRhein GM et al (1971) Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1:1257–1260

    Article  CAS  PubMed  Google Scholar 

  19. Sastre-Garau X, Peter M, Avril MF et al (2009) Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis. J Pathol 218:48–56

    Article  CAS  PubMed  Google Scholar 

  20. Shuda M, Feng H, Kwun HJ et al (2008) T-antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci U S A 105:16277

    Article  CAS  Google Scholar 

  21. Swann MH, Yoon J (2007) Merkel cell carcinoma. Semin Oncol 34:51–56

    Article  PubMed  Google Scholar 

  22. Sweet BH, Hillemann MR (1960) The vacuolating virus, S.V. 40. Proc Soc Exp Biol Med 105:420–427

    CAS  PubMed  Google Scholar 

  23. Toker C (1972) Trabecular carcinoma of the skin. Arch Dermatol 105:107–110

    Article  CAS  PubMed  Google Scholar 

  24. Urbatsch A, Sams WM Jr, Urist MM, Sturdivant R (1999) Merkel cell carcinoma occurring in renal transplant patients. J Am Acad Dermatol 41:289–291

    Article  CAS  PubMed  Google Scholar 

  25. Wieland U, Mauch C, Kreuter A et al (2009) Merkel cell polyomavirus DNA in persons without merkel cell carcinoma. Emerg Infect Dis 15:1496–1498

    Article  CAS  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinikum Freiburg, Breisacherstr. 115 A, 79106, Freiburg, Deutschland

    A. zur Hausen

Authors
  1. A. zur Hausen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. zur Hausen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

zur Hausen, A. Das Merkel-Zell-Polyomavirus in der Pathogenese nichtmelanozytärer Hauttumoren. Pathologe 30 (Suppl 2), 217–220 (2009). https://doi.org/10.1007/s00292-009-1222-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-009-1222-4

Schlüsselwörter

Keywords

Search

Navigation