Lack of evidence for an association of Epstein-Barr virus infection with breast carcinoma

Abstract

Background: Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpes virus infecting more than 90% of the population worldwide. EBV is associated with certain malignancies (e.g. Burkitt lymphoma, Hodgkin lymphoma and nasopharyngeal carcinoma). Recent studies have raised the possibility that EBV may also be involved in the pathogenesis of breast carcinoma, the most common carcinoma of females. If substantiated, this finding would have major implications regarding prevention and therapy of the disease. The studies published so far have employed diverse methods, however, and the results have been controversial.

Methods: Using the EBV DNA PCR, EBV DNA in situ hybridisation and in situ hybridisation for the detection of the EBV-encoded RNAs, and using immunohistochemistry for the demonstration of the EBV-encoded nuclear antigen 1, we have studied a series of 59 invasive breast carcinomas for evidence of EBV infection.

Results: EBV-encoded RNA-specific in situ hybridisation and EBV-encoded nuclear antigen 1 immunohistochemistry were negative in all cases. Using the PCR, EBV DNA was detected in four out of 59 cases. These cases were further studied by EBV DNA in situ hybridisation, showing an absence of viral DNA from the tumour cells.

Conclusion: These results indicate that breast carcinoma is not an EBV-associated tumour.

Figure 1

In situ detection of Epstein–Barr virus (EBV) in breast carcinomas. In situ hybridisation with ³⁵S-labelled RNA probes shows (a) an absence of expression of the EBV-encoded RNAs (EBERs) in a breast carcinoma (note an isolated EBER-positive lymphocyte in the tumour stroma; black grains, arrow), while (b) tumour cells of a nasopharyngeal carcinoma show a strong nuclear labelling indicating EBER expression (black grains). Immunohistochemistry reveals (c) an absence of detectable expression of the EBV-encoded nuclear antigen1 (EBNA1) in a breast carcinoma and (d) the expression of EBNA1 in most nasopharyngeal carcinoma cells (red nuclear staining). Using DNA in situ hybridisation with ³⁵S-labelled probes, (e) an absence of EBV from breast carcinoma cells is demonstrated while (f) EBV DNA is detected in tumour cells of an undifferentiated nasopharyngeal carcinoma (black grains).