Introduction: Epstein-Barr virus is a ubiquitous human herpes virus in the Hungarian population. The virus is associated with an increasing number of lymphoid malignancies, such as Hodgkin and non-Hodgkin lymphomas. The ability of the virus to establish life-long persistent infection and induce growth transformation is related to the viral proteins that are variously expressed in both normal and malignant cells. Although the presence of ZEBRA protein induces lytic cycle, some lymphoma cases show this protein expression.
Aim: In our present study we investigated the frequency of expression of ZEBRA protein in Hungarian patients with Hodgkin lymphoma associated with Epstein-Barr virus infection. The authors wanted to clarify whether this expression is specific to latency type II or occurs in some non-Hodgkin lymphoma cases with latency type III as well. Does the expression of ZEBRA protein have any effect on therapeutic response and survival rate of the patients?
Method: 109 HL and 59 NHL were studied for the presence of the virus in the tumor and for expression of the latency proteins and ZEBRA by immunohistochemistry.
Results: 25 samples were evaluated successfully for ZEBRA of the 47 LMP1 positive HL samples. We detected the weak expression of ZEBRA protein in 13 of the 25 LMP1 positive Hodgkin lymphoma cases and in 6 of the 18 LMP1 positive non-Hodgkin lymphoma samples. The authors could not find correlation between the expression of ZEBRA protein and the type of latency. During the followed 120 months the total survival of patients with ZEBRA positivity proved to be significantly shorter as compared to that of ZEBRA negative cases. The authors could not find significant difference in the uneventful survival of these two groups.
Conclusion: In the examined group of patients the ZEBRA positivity associated with a poor prognosis of the disease. Besides this relatively small number of cases, additional extensive studies are needed to conclude our observation. Elucidation of the switching mechanisms by which Epstein-Barr virus induces lytic cycle may provide an efficacious therapeutic approach to the EBV-related malignancies.