title: No significant association of Epstein-Barr virus infection with invasive breast carcinoma.
abstract: We studied 48 cases of invasive breast carcinoma for evidence of Epstein-Barr virus (EBV), which is associated with many human malignancies. In situ hybridization studies to detect the presence of EBV-encoded small nonpolyadenylated RNA (EBER)-1 were performed in paraffin sections. Immunohistochemical 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 studied by polymerase chain reaction (PCR) amplification using sets of primers 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 then attempted in cases that were PCR-positive. Five of 48 cases (10%) of breast carcinoma showed focal EBER-positive tumor cells. Twelve cases (25%) were positive for EBNA-1 by immunohistochemistry, all but one different from the 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, Southern blot studies successfully performed in all but one of the PCR-positive cases were completely negative. The identification of EBV by any methodology was not correlated with tumor size, grade, or lymph node status. This study demonstrated evidence of EBV infection in tissues involved by invasive breast carcinomas in a significant subset of cases. However, the lack of localization of EBV infection to a significant population of the tumor cells in any case, the negativity by Southern blot hybridization, and the lack of expression of multiple antigens in any case strongly argue against a significant role for EBV in the pathogenesis of breast carcinoma.
authors.affiliation: Division of Pathology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA. pchu@coh.org
authors.forename: P G
authors.initials: PG
authors.lastname: Chu
authors.forename: K L
authors.initials: KL
authors.lastname: Chang
authors.forename: Y Y
authors.initials: YY
authors.lastname: Chen
authors.forename: W G
authors.initials: WG
authors.lastname: Chen
authors.forename: L M
authors.initials: LM
authors.lastname: Weiss
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000473:pathology* / Q000821:virology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology / Q000821:virology; D018275:Carcinoma, Lobular / Q000473:pathology / Q000821:virology; D002352:Carrier Proteins / Q000032:analysis; D003598:Cytoskeletal Proteins; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D019309:Epstein-Barr Virus Nuclear Antigens / Q000032:analysis; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis*; D012189:Retrospective Studies; D015534:Trans-Activators / Q000032:analysis; D014764:Viral Proteins / Q000032:analysis; D016335:Zinc Fingers
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C063676:BZLF1 protein, Herpesvirus 4, Human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human; D012367:RNA, Viral; D015534:Trans-Activators; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1