Detection Of EBV And HTLV-1in Peripheral T-cell Lymphomas And Analysis

OBJECTIVE:Peripheral T-cell lymphomas (PTCL) are uncommon malignancies derived from mature T cells and natural killer (NK) cells at different steps of differentiation, altogether accounting for<15%of all non-Hodgkin’s lymphoma (NHL) worldwide. They are diverse group of disorders that carry a poor prognosis. According to the new World Health Organization (WHO) classification, they are subdivided into specified and unspecified forms. The overall incidence of PTCL is higher in Asia and Central/South America than in Western countries, especially that of those induced by HTLV-I and by EBV.EBV was discovered in1964in African Burkitt lymphoma cell cultures. And EBV is one of the human herpes DNA viruses and is known to be involved in the development of malignant lymphoma such as Burkitt’s lymphoma, Hodgkin’s lymphoma (HL) and T-cell non-Hodgkin’s lymphoma (NHL). HTLV, the first human retrovirus to be identified, can cause adult T-cell leukemia/lymphoma (ATLL) and other diseases. The increased incidence of T cell lymphoma in East Asia related to the frequency of endemic HTLV-I and EBV infection. And Hainan is also a T-cell lymphoma endemic area. According to seroepidemiology investigation in China, HTLV-1infections are usually found in Fujian and Guangdong provinces, China’s southeast coastal regions. Given the similar coastal geographical environment, Hainan district lacks the epidemiological study of HTLV-I. And EBV infection is relative common in Hainan. The high incidence of T cell lymphoma in Hainan may be closely related to HTLV-1and EBV. In addition, the interaction of these two oncoviruses has seldom been reported in the medical literature. So we investigated the presence of EBV and HTLV-I in PTCL using EBER-1in situ hybridization (ISH) and polymerase chain reaction (PCR) techniques.METHODS:46cases of Formalin-fixed paraffin-embedded Peripheral T-cell lymphomas tissues were collected from malignant lymphoma. By using labeled streptavidin biotin method (MAXIN.Bio), immunohistochemistry studies were performed using the following primary antibodies:TdT, CD20、 CD3、 CD4、 CD8、 CD56、 CD30、 CD45RO、TIA-1. EBV and HTLV-1were detected respectively by in situ hybridization and polymerase chain reaction (PCR) in46cases of Formalin-fixed paraffin-embedded Peripheral T-cell lymphomas tissuesand30cases of normal samples.RESULTS:(1) Histology type and immunophenotype:according to the WHO classification, in46cases,20cases (43.5%) were confirmed as Peripheral T-cell lymphomas, unspecified,12cases (26.1%) were NK/T cell lymphoma,10cases (21.7%) were Cutaneous T-cell Lymphoma(CTCL) and4cases (8.7%) were Adult T-cell lymphoma/leukemia (ATLL).(2) EBV:EBER-1ISH was performed to detect EBV and brown granular nucleus staining as a positive signal. EBV-infected cells were detected in26(56.52%) of46PTCL cases;9(45.0%) of20cases of Peripheral T, not characterized,10(83.3%) of12cases of NK/T cell lymphoma,5(50.0%) of10cases of CTCL,2(50.0%) of4cases of ATLL. The ISH products of30normarl samples were all negative.(3) HTLV-1:HTLV-I was detected in8(17.4%) of46PTCL cases;3(15.0%) of20cases of Peripheral T, not characterized,1(8.3%) of11cases of NK/T cell lymphoma,1(10%) of10cases of CTCL,3(75.0%) of4cases of ATLL. The PCR products of30normarl samples were all negative.CONCLUSIONS:The EBV-infected cells were detected in26(56.5%) of46PTCL by EBER-1in situ hybridization (EBER-1ISH). Using polymerase chain reaction (PCR), HTLV-1was detected in8(17.4%) of46PTCL. The previous research has shown that EBV was involved in the development of NK/T cell lymphoma and HTLV-1can cause ATLL. However, in our study, EBV and HTLV-1can be detected in all types of PTCL that we can collect. Accidentally,4cases were co-infected by EBV and HTLV-1. We can speculate that the combination of EBV and HTLV-1co-infection and immunodeficiency may have played a role in the development of certain type of PTCL.