No significant association of Epstein-Barr virus infection with invasive breast carcinoma

We studied 48 cases of invasive breast carcinoma for evidence of Epstein-Ba rr virus (EBV), which is associated with many human malignancies. In situ h ybridization studies to detect the presence of EBV-encoded small nonpolyade nylated RNA (EBER)-1 were performed in paraffin sections. Immunohistochemic al studies to detect EBV nuclear antigen (EBNA)-1, latent membrane protein (LMP)-1, and the transactivating immediate-early BZLF1 (ZEBRA) protein were also performed in paraffin sections. The presence of EBV genomic DNA was s tudied by polymerase chain reaction (PCR) amplification using sets of prime rs flanking the EBNA-4 and the EBV-LMP-1 genes in frozen tissues. Southern blot analysis using a probe flanking the EBV terminal repeat region was the n attempted in cases that were PCR-positive. Five of 48 cases (10%) of brea st carcinoma showed focal EBER-positive tumor cells. Twelve cases (25%) wer e positive for EBNA-1 by immunohistochemistry, all but one different from t he EBER-positive cases. None of the cases were positive for LMP-1 or ZEBRA protein by immunohistochemistry. PCR studies for EBNA-4 and LMP-1 were each positive in five cases (including three cases in common). However, Souther n blot studies successfully performed in all but one of the MR-positive cas es were completely negative. The identification of EBV by any methodology w as not correlated with tumor size, grade, or lymph node status. This study demonstrated evidence of EBV infection in tissues involved by invasive brea st carcinomas in a significant subset of cases. However, the lack of locali zation of EBV infection to a significant population of the tumor cells in a ny case, the negativity by Southern blot hybridization, and the lack of exp ression of multiple antigens in any case strongly argue against a significa nt role for EBV in the pathogenesis of breast carcinoma.