EBER1 Small Nuclear RNA in Malignancy: A Morphologically Distinctive Target for Detection of EBV in Formalin-Fixed Paraffin-Embedded Specimens

Abstract

EBV is a ubiquitous virus which is consistently detected in nasopharyngeal carcinoma (NPC), African Burkitt’s lymphoma, post-transplant lymphoma and is frequently detected in HIV-associated lymphoma and Hodgkin’s disease (1–3). Detection of the virus in archival formalin-fixed paraffin embedded clinical specimens has been difficult because of limited EBV gene expression, particularly in latently infected malignant cells. EBV antigen detection has not been reliable in paraffin sections and the only antigen expressed in each of the various EBVassociated malignancies, EBNA-1 cannot be detected in paraffin at all. Polymerase chain reaction amplification is possible but cannot provide cellular localization (4). In situ hybridization offers a promising alternative, but in latent infection EBV copy numbers are low and gene expression is highly restricted. We reasoned that the EBER RNAs, whose abundance in lymphoblastoid cell lines has been estimated to be 10⁷ copies per cell, should be greatly superior to other latency transcripts as targets for in situ hybridization (5–8).