© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 16, 1376-1381,
August 18, 1999
© 1999 Oxford University Press
Detection of Epstein-Barr Virus in Invasive Breast Cancers
Affiliations of authors: M. Bonnet, I. Joab, Institut National de la Santé et de la Recherche Médicale, EPI 99-32, Pharmacologie Expérimentale et Clinique, Hôpital Saint Louis, Institut de Génétique Moléculaire, Paris, France, and Centre National de la Recherche Scientifique (CNRS) URA 1301, Institut Gustave Roussy, Villejuif, France; J.-M. Guinebretiere, G. Contesso, Department of Pathology, Institut Gustave Roussy; E. Kremmer, Forschungszentrum für Umwelt und Gesundheit GmbH, Institut für Immunologie, Munchen, Germany; V. Grunewald, CNRS URA 1301, Institut Gustave Roussy; E. Benhamou, Department of Biostatistics and Epidemiology, Institut Gustave Roussy.
Correspondence to: Irene Joab, Ph.D., Institut de Génétique Moleculaire, Pharmacologie Expérimentale et Clinique, IFR Saint Louis, 27 Rue Juliette Dodu, 75010, Paris, France (e-mail: i.joab{at}chu-stlouis.fr).
BACKGROUND: Epstein-Barr virus (EBV) may be a cofactor in the development of different malignancies, including several types of carcinomas. In this study, we investigated the presence of EBV in human breast cancers. METHODS: We used tissues from 100 consecutive primary invasive breast carcinomas, as well as 30 healthy tissues adjacent to a subset of the tumors. DNA was amplified by use of the polymerase chain reaction (PCR), with the primers covering three different regions of the EBV genome. Southern blot analysis was performed by use of a labeled EBV BamHI W restriction fragment as the probe. Infected cells were identified by means of immunohistochemical staining, using monoclonal antibodies directed against the EBV nuclear protein EBNA-1. RESULTS: We were able to detect the EBV genome by PCR in 51% of the tumors, whereas, in 90% of the cases studied, the virus was not detected in healthy tissue adjacent to the tumor (P<.001). The presence of the EBV genome in breast tumors was confirmed by Southern blot analysis. The observed EBNA-1 expression was restricted to a fraction (5%-30%) of tumor epithelial cells. Moreover, no immunohistochemical staining was observed in tumors that were negative for EBV by PCR. EBV was detected more frequently in breast tumors that were hormone-receptor negative (P = .01) and those of high histologic grade (P = .03). EBV detection in primary tumors varied by nodal status (P = .01), largely because of the difference between subjects with more than three lymph nodes versus less than or equal to three lymph nodes involved (72% versus 44%). CONCLUSIONS: Our results demonstrated the presence of the EBV genome in a large subset of breast cancers. The virus was restricted to tumor cells and was more frequently associated with the most aggressive tumors. EBV may be a cofactor in the development of some breast cancers.
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