Demonstration of Epstein Barr virus in breast carcinomas

PRECIADO, M. V.; PAOLA ANDREA CHABAY; GASS, H.; DE MATTEO, E; GONZALEZ, P.; FERRERO, A.; ACTIIS, A.; ROMERO, R.; GRINSTEIN, S.

San Francisco

Congreso; 93th Annual Meeting of the American Association for Cancer Research; 2002

American Associaton for Cancer Research

Background: Epstein Barr virus (EBV), an ubiquitous herpes virus, is associated to the development of several malignancies such as Burkitt´s lymphoma, Hodgkin´s lymphoma, B cell lymphoma in immunocompromised patients, nasopharyngeal carcinoma and more recently to some gastric and lung carcinomas. In Argentina, first EBV infection usually occurs in children under six years of age, meanwhile in USA it occurs in adolescents. As breast cancer is a very common malignancy in women, a pathogenetic role of EBV for even a subgroup of patients could have important significance for its etiology and prevention. Our aim was to confirm EBV breast carcinoma association and to correlate breast carcinoma risk and delayed primary EBV infection. Methods: We analyzed formalin-fixed paraffin-embedded breast biopsies of 53 Argentine and 33 American patients with primary invasive breast carcinoma. We also obtained fresh tissue of 23/53 from the former. The age ranged from 35 to 96 years (median: 60 years). Argentine cases were classified by age (<=50 or >50 years), tumor histology (ductal: grade I, II, III or lobular), clinical stage (I, II, III, IV), lymph node metastasis (present or absent) and estrogen receptor status (positive or negative). EBV infected cells were identified by means of immunohistochemistry (IHQ), using a monoclonal antibody directed against EBV nuclear antigen1 (EBNA1) in 86 cases and DNA was amplified by use of PCR , with primers covering EBERs region of the EBV genome in a subset of 23 cases. Results: EBNA1 granular nuclear expression was observed in a fraction (5-40%) of tumor epithelial cells in 17/53 (32%) of Argentine cases and in 14/33 (42%) American ones. One American case showing a focus of in situ carcinoma also showed focal nuclear staining. We confirmed both positive and negative IHQ results by PCR in those cases where good quality DNA was also available, detecting an amplification fragment of 108bp corresponding to an EBERs region. Among Argentine patients EBV was more frequently detected in breast carcinomas that were estrogen receptor positive (12/33, 36%), those without lymph node metastasis (9/22, 41%) and those of postmenopausal women (12/38, 32%) but none of this associations were statistically significant. The proportion of EBV positive samples was similar in the three histologic grades with 32%, 32% and 21% for grade I, II and III respectively. EBV receptor, CD21, was negative in all the breast carcinomas studied. Conclusions: Our results demonstrated the presence and expression of EBV restricted to epithelial tumor cells in a large subset of breast carcinomas. EBV-breast carcinoma association in the American group (42%) was higher than the one in the Argentine (32%) group. These data strength the idea of the association between breast carcinoma risk and delayed EBV primary infection. However, the role of EBV in breast carcinomas remains to be clarified and the clinical implications of the presence of EBV need further studies.