[Infectious agents in ocular adnexal tumours]

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.