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Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells
H Herbst1, F Dallenbach, M Hummel
1Institute of Pathology, Klinikum Steglitz, Free University of Berlin, Federal Republic of Germany.
Abstract:
Cryostat sections from lymph nodes of 47 Hodgkin disease patients were examined by immunohistology for the Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP), nuclear antigen 2, and late viral glycoprotein gp350/250. A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in Hodgkin and Reed-Sternberg cells in 18 patients (38%); EBV nuclear antigen 2 and gp350/250 immunoreactivity was absent in all instances. Thirty-two of 47 (68%) cases contained EBV-specific DNA sequences as detected by PCR, all LMP-positive cases being in this category. Our results confirm previous studies establishing the presence of EBV genomes in Hodgkin and Reed-Sternberg cells by demonstrating expression of an EBV-encoded protein in the tumor-cell population. The finding of LMP expression in the absence of EBV nuclear antigen 2 suggests a pattern of EBV gene expression different from that of B-lymphoblastoid cell lines and Burkitt lymphoma, whereas this finding shows similarities with that seen in undifferentiated nasopharyngeal carcinoma. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiological role of EBV in many cases of Hodgkin disease.
Insights
Epstein-Barr virus (EBV) latent membrane protein (LMP) was found in tumor cells of 38% of Hodgkin disease patients. This suggests EBV plays a role in Hodgkin disease pathogenesis.
Area of Science:
- Oncology
- Virology
- Immunohistochemistry
Background:
- Hodgkin disease is a malignancy of lymphocytes.
- Epstein-Barr virus (EBV) is implicated in the pathogenesis of some Hodgkin disease cases.
- The specific EBV proteins expressed in Hodgkin and Reed-Sternberg cells remain incompletely understood.
Purpose of the Study:
- To investigate the expression of EBV-encoded latent membrane protein (LMP), nuclear antigen 2, and glycoprotein gp350/250 in Hodgkin disease.
- To determine the correlation between EBV presence and specific viral protein expression in tumor cells.
- To elucidate the pattern of EBV gene expression in Hodgkin disease.
Main Methods:
- Immunohistochemistry was used to detect EBV proteins (LMP, EBNA2, gp350/250) in cryostat sections of lymph nodes from 47 Hodgkin disease patients.
- Polymerase chain reaction (PCR) was employed to detect EBV-specific DNA sequences.
Main Results:
- Distinct LMP-specific staining was observed in the membrane and cytoplasm of Hodgkin and Reed-Sternberg cells in 18 out of 47 patients (38%).
- EBV nuclear antigen 2 and gp350/250 immunoreactivity were absent in all examined cases.
- EBV DNA sequences were detected in 32 out of 47 cases (68%), with all LMP-positive cases containing EBV DNA.
Conclusions:
- The study confirms the presence of EBV genomes in Hodgkin and Reed-Sternberg cells by demonstrating the expression of an EBV-encoded protein (LMP).
- The observed expression pattern of LMP without EBNA2 differs from B-lymphoblastoid cell lines and Burkitt lymphoma but resembles undifferentiated nasopharyngeal carcinoma.
- The findings support a pathoetiological role for EBV in a significant subset of Hodgkin disease cases, potentially mediated by the transforming potential of LMP.