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Klin Monbl Augenheilkd 2010; 227(7): 530-537
DOI: 10.1055/s-0029-1245153
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Erreger bei Tumoren der okulären Adnexe

Infectious Agents in Ocular Adnexal TumoursC. Auw-Hädrich1 , N. Göbel1 , G. Illerhaus2
  • 1Allgemeine Augenheilkunde, Universitäts-Augenklinik, Freiburg
  • 2Hämatologie und Onkologie, Medizinische Klinik, Freiburg
Further Information

Publication History

Eingegangen: 7.9.2009

Angenommen: 18.1.2010

Publication Date:
09 June 2010 (online)

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Zusammenfassung

In den vergangenen Jahren wurden Erreger zunehmend als ein wichtiger pathogenetischer Faktor verschiedener maligner Tumoren der okulären Adnexe erkannt. Viele dieser Viren und Bakterien beeinflussen den Zellzyklus und die physiologische Apoptose. Lymphome der okulären Adnexe, insbesondere das extranodale Marginalzonenlymphom, werden in manchen Regionen durch Chlamydophila psittaci und Helicobacter pylori verursacht. Epstein-Barr-Viren scheinen bei dem Natural-Killer/T-Zell-Lymphom-Subtyp eine Rolle zu spielen, wie sie bei dem Burkitt-Lymphom bereits länger bekannt ist. Bakterien scheinen eine reaktive lymphoide Proliferation zu induzieren, während Viren direkt die lymphoiden Zellen befallen und den Zellzyklus beeinflussen und die Apoptose unterdrücken mit der nachfolgenden malignen Entartung. Im Allgemeinen sind Proteine, die zur Zellzyklusprogression führen, wie z. B. das Retinoblastomprotein, erhöht und Eiweiße, die den Zellzyklusfortgang unterdrücken (wie z. B. p16 und p21) abwesend oder funktionsuntüchtig. Die Inaktivierung von p53 durch Mutation seines Gens führt zu einer Erhöhung eines defekten p53 Proteins und zur Einschränkung der Apoptose, wodurch die onkogenen Zufallsmutationen wirksam werden können. Die konjunktivale intraepitheliale Neoplasie (CIN) ist im Vergleich zu dem Pendant der Zervix, der zervikalen intraepithelialen Neoplasie, weniger häufig mit einer HPV-Infektion verbunden. Aufgrund der CIN-Lokalisation scheinen besonders UVB-Strahlen eine Rolle bei ihrer Entstehung zu spielen, wodurch es zu einer p53-Inaktivierung und nachfolgender Hemmung der Apoptose kommt. HIV-Positivität scheint ebenfalls die Entwicklung von CIN und Bindehautkarzinomen zu begünstigen, in den letzten Jahren mit zunehmender Fallzahl. Das Kaposi-Sarkom tritt bei HIV-infizierten Personen selten an der okulären Adnexe auf und scheint mit dem kaposi-sarkomaassoziierten Herpes-Virus (KSHV) oder HHV8 zusammenzuhängen. Das KSHV-assoziierte Latency Associated Nuclear Antigen (LANA) Protein bindet an den negativen Regulator Glycogen-Synthase Kinase-3 (GSK-3), und bedingt im Kern eine zellzyklusabhängige Ansammlung von GSK-3, welches Beta-Catenin stabilisiert und seine Konzentration erhöht. Die neuen Erkenntnisse über diese verschiedenartigen Erreger und Zellzyklusbeeinträchtigungen mögen einen Einfluss auf die Entwicklung neuer therapeutischer Strategien haben.

Abstract

In recent years, infectious agents have been increasingly recognised as an important pathogenetic factor for various malignant tumours of the ocular adnexa. Many of these viruses and bacteria affect the cell cycle and physiological apoptosis. Ocular adnexal lymphoma (OAL), especially extranodal marginal cell lymphoma, is associated with Chlamydophila psittaci and Helicobacter pylori in certain geographic regions. Epstein-Barr virus seems to play a role in the natural killer/T-cell lymphoma subtype of the orbit, as has long been described for Burkitt lymphoma. Bacteria seem to induce reactive lymphoid proliferation, while viruses directly infect the lymphoid cells, affecting the cell cycle and suppressing apoptosis, with subsequent malignant transformation. In general, proteins leading to cell cycle progression, like retinoblastoma protein, are elevated, and proteins inhibiting cell cycle progression, like p16 and p21, are absent or unable to function normally. Inactivation of p53 by mutation of its DNA, which leads to elevation of defective p53 protein and inhibition of apoptosis, allows oncogenic by-chance mutations to become effective. Conjunctival intraepithelial neoplasia (CIN) is less strongly associated with HPV infection than is cervical intraepithelial neoplasia. Based on the localisation of CIN, ultraviolet B radiation seems to play a primary role, leading to p53 inactivation and subsequent inhibition of apoptosis. HIV positivity also seems to aid the development of CIN and conjunctival squamous cell carcinoma, with an increasing number of cases during recent years. Kaposi sarcoma rarely occurs at the ocular adnexa in HIV-positive individuals and seems to be associated with Kaposi sarcoma-associated Herpes virus (KSHV) or HHV8. The KSHV-encoded latency associated nuclear antigen (LANA) protein binds to the negative regulator glycogen-synthase kinase-3 (GSK-3), causing a cell cycle-dependent nuclear accumulation of GSK-3, which stabilises beta-catenin and increases its levels. The findings regarding these various infectious agents and cell cycle alterations might aid the development of new therapeutic strategies.

Schlüsselwörter

okuläre Tumoren - Pharmakologie - Infektiologie

Key words

pharmacology - ocular tumours - infectious diseases

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Prof. Dr. Claudia Auw-Hädrich

Universitäts-Augenklinik Freiburg

Killianstr. 5

79106 Freiburg

Phone: ++ 49/7 61/2 70 41 95

Fax: ++ 49/7 61/2 70 40 57

Email: claudia.auw-haedrich@uniklinik-freiburg.de