Expression of Epstein-Barr virus-encoded RNAs as a marker for metastatic undifferentiated nasopharyngeal carcinoma

BACKGROUND. Epstein-Barr virus (EBX) is associated with undifferentiated nasopharyngeal carcinoma (NPC). EBV-encoded nonpolyadenylated RNAs (EBERs) are often used as a marker to detect EBV-infected NPC cells. This study was conducted to document the expression and determine the significance of EBERs in NPC cells at various metastatic sites. METHODS. An in situ hybridization (ISH) technique was used to identify the presence of EBERs in paraffin embedded tissues of primary and metastatic sites obtained from 21 patients with NPC. Nineteen of these patients had undifferentiated lesions, and 2 had squamous cell carcinoma. One hundred and fifty specimens of normal tissues and tissues from patients with a variety of benign and malignant diseases other than NPC served as controls. In the NPC specimens, the expression of latent membrane protein (LMP) and a lytic protein, BZLF-1, were also examined by immunohistochemistry. RESULTS. Tissues from all patients with undifferentiated NPC and one patient with squamous cell carcinoma contained EBERs in the malignant cells; the other case of squamous cell carcinoma was negative. In metastatic NPCs, LMP was expressed in 18% (4 of 22) of tissues whereas BZLF-1 was not expressed in any tissues. EBERs were not detected in the 43 patients with normal tissues and benign lesions. In malignant diseases other than NPC. EBERs were detected in only 2 of 12 cases of non-Hodgkin's lymphoma, 1 of 2 cases of Hodgkin's lymphoma, anti 1 of 6 cases of gastric cancer. CONCLUSIONS. By virtue of the direct correlation between latent EBV infection and NPC, the authors conclude that EBERs can be used as a sensitive marker to identify NPC cells at various metastatic sites by techniques of in situ hybridization, and that demonstration of EBERs in lesions of undifferentiated histology may be useful as a diagnostic adjunct for NPC presenting as metastatic cancer of unknown origin.