Differential expression of EBV proteins LMP1 and BHFR1 in EBV‑associated gastric and nasopharyngeal cancer tissues.

Abstract

Epstein-Barr virus (EBV) infection is associated with the development of T cell lymphoma, nasopharyngeal cancer (NPC), and EBV-associated gastric cancer (EBVaGC). This study assessed the expression of the EBV-associated proteins latent membrane protein 1 (LMP1) and BamHI-A rightward frame 1 (BARF1) in NPC and EBVaGC tissue specimens and determined their association with clinicopathological data, microvessel density (MVD) and micro-lymphatic vessel density (MLVD). This study collected 600 gastric cancer and 75 NPC tissue samples. EBV infection was assessed using in situ hybridization, and LMP1 and BARF1 expression was assessed using immunohistochemistry. The levels of MVD and MLVD were assessed using immunostaining of vascular endothelial growth factor (VEGF)-C, CD34, and lymphatic vessel endothelial receptor 1 (LYVE-1). Among the 600 gastric cancer cases, 30 were positive for EBV infection, which was shown to be associated with the age of patients (P=0.073), tumor differentiation (P<0.0001), tumor location (P<0.0001) and lymph node metastasis (P<0.0001). In these 30 EBVaGC cases, only one case was weakly positive for LMP1, but 17 cases were BARF1 positive. BARF1 expression was associated with lymph node metastasis of EBVaGC and the level of MLVD. Furthermore, 61 (81%) of 75 NPC patients were EBV positive, among which 38 cases were LMP-1 positive (62.3%) and LMP1 expression was associated with tumor-node-metastasis stage (P=0.011) and lymph node metastasis (P=0.041). MLVD was significantly higher in LMP1-positive cases than LMP1-negative cases. There were only 8 (13.3%) cases positive for BARF1 expression. In conclusion, EBV infection exhibits a role in gastric cancer and NPC development; however, expression of EBV-associated proteins LMP1 and BARF1 have differential functions during tumorigenesis of these two types of cancer.