Localization of Epstein-Barr virus to infiltrating lymphocytes in breast carcinomas and not malignant cells

The pathogenesis of breast cancer is unknown. In recent years, a number of studies have implicated a role for Epstein-Barr virus (EBV) in a subset of cases. However, these findings are controversial and others have failed to find any link between the virus and this malignancy. We hypothesized that technical differences and the different type and ethnic origin of the cases may be the cause of the disparities reported. Using a highly sensitive EBER-in situ hybridization and immunohistochemistry, we examined 219 samples (158 malignant and 61 non-malignant) from 61 Emirati breast cancer cases to determine if EBV was etiologically associated with Emirati cases and if there was any correlation with other established prognostic factors such as age, histological type, lymph node metastasis, estrogen, progesterone and HER2 expression. We found 47.5% of the cases to be EBV positive, but the virus was localized to occasional infiltrating lymphocytes and not in the malignant cells. EBV lymphocytes were more commonly observed in lymph nodes than in breast tissues, but there was no correlation with malignancy or hormone status. The mean age of our patients was 48 years and hormone receptor staining revealed 20% of the cases to be triple negative (ER−/PR−/HER2−). We conclude that although EBV can be detected in breast cancer cases, it is not directly associated with the disease. Thus, a PCR-based approach cannot be used to link this ubiquitous virus to the pathogenesis of breast cancer. Furthermore, we do not find any correlation between the presence of EBV in infiltrating lymphocytes and ER, PR, HER2 expression. We believe our findings will help explain some of the controversies relating to the role of EBV in the pathogenesis of breast cancer.