EB virus (EBV), also known as human herpesvirus 4, is a lymphotropic DNA virus, with humans being its only host. Over 90% of individuals are infected with EB virus before the age of 20, with most showing asymptomatic infection or self-limiting infectious mononucleosis (IM), which is also a common adenovirus-like fever similar to a cold. However, a small number of people may develop non-neoplastic severe EBV-related diseases such as chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). However, EBV can also remain latent in certain cells of the immune system, and a small number of carriers may develop cancer after long-term carriage, such as Hodgkin lymphoma, non-Hodgkin lymphoma, nasopharyngeal carcinoma, gastric cancer, post-transplant lymphoproliferative disorders, etc. Some studies also suggest that EBV may only be a triggering factor rather than the main cause.
The gene expression products of EBV during latent infection can promote the occurrence of lymphoma, leading to hematological system-related tumors such as Burkitt lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, NK/T-cell lymphoma, post-transplant lymphoproliferative disorders, and X-linked lymphoproliferative disease. EBV-associated hemophagocytic lymphohistiocytosis is often fulminant and has a very poor prognosis.
【Nasopharyngeal Carcinoma】
Nasopharyngeal carcinoma is also a common epithelial cell malignancy closely related to EBV. In some nasopharyngeal carcinoma patients, EBV persistently infects nasopharyngeal epithelial cells. Studies have found that EBV DNA is almost 100% present in the primary tumors and metastatic lesions of nasopharyngeal carcinoma, so EBV-encoded proteins are commonly used clinical tumor markers for nasopharyngeal carcinoma.
EBV-associated gastric cancer (EBVaGC) is considered by most studies to be an independent subtype of gastric cancer due to its unique molecular biological characteristics. In China, EBVaGC accounts for about 7-10% of all gastric cancers. Most studies show that the prognosis of EBVaGC patients is significantly better than that of EBV-negative gastric cancer, and the primary tumors of EBVaGC patients are smaller in volume, with a lower proportion of distant metastasis.
Numerous studies have confirmed that leiomyosarcoma is closely related to EBV infection, and EBV-associated leiomyosarcoma is generally combined with HIV infection or organ transplantation. For leiomyosarcoma patients, EBV-associated leiomyosarcoma has a better prognosis, while non-EBV-associated leiomyosarcoma is often accompanied by hematogenous dissemination and distant metastasis. In EBV-associated leiomyosarcoma, tumor-related deaths account for only 6%.
There are many methods currently used to detect EBV, but in tumor diagnosis, serological detection of EBV can only serve as evidence suggesting the presence of EBV. Immunohistochemistry and in situ hybridization detection are the ‘gold standards’ for pathological diagnosis of EBV, not only aiding in tumor diagnosis and differentiation but also helping to understand prognosis and guide treatment.
【Immunohistochemistry Method】
EBV latent membrane protein 1 (LMP-1) is recognized as a viral genome-encoded oncoprotein that promotes cell carcinogenesis and metastasis, and it is the only EBV-encoded gene product capable of transforming cells in vitro.LMP-1 can be detected by immunohistochemistry.This method can stain the cytoplasm and cell membrane, thus objectively showing the protein expression of EBV in infected cells. Immunohistochemistry can only detect the stage of viral protein expression and has slightly lower sensitivity for detecting low-copy EBV within cells.
【In Situ Hybridization Method】
In situ hybridization for detecting EBER is considered the gold standard for detecting EBV in tumor cells, with high sensitivity and specificity. EBER staining colors the nucleus, providing clear and easily recognizable results, reflecting DNA transcription. EBER in situ hybridization has high sensitivity and specificity, with clear tissue localization,making it the gold standard for detecting EBV infection.
