Expression of EBER1 in primary and metastatic nasopharyngeal carcinoma tissues using in situ hybridization. A correlation with WHO histologic subtypes.

BACKGROUND

The association of Epstein-Barr virus (EBV) with nasopharyngeal carcinoma (NPC) is well documented. Previous studies reported abundant expression of EBER1 in primary NPC and tumors metastatic to lymph nodes. However, a large series of case studies correlating World Health Organization (WHO) histologic subtypes with EBER1 is needed.

METHODS

The authors applied the EBER1 in situ hybridization to investigate the expression of EBER1 in 140 primary NPCs, 11 metastatic tumors to lymph nodes, 6 metastatic tumors to bone marrow, and 2 metastatic tumors to the liver. All 19 metastatic tumors had paired specimens from their primary NPCs for comparison. The in situ hybridization method was performed on paraffin embedded tissues by using polymerase chain reaction-derived, digoxigenin-labelled EBER1 DNA probes.

RESULTS

The EBER1 signal was identified in nuclei of malignant epithelial cells in 135 of 140 (96.4%) primary NPCs, including 4 of 5 (80%) WHO-I histologic subtypes, 71 of 73 (97.3%) WHO-II histologic subtypes, and 60 of 62 (96.8%) WHO-III histologic subtypes (P > 0.05). However, the positive hybridization signal in WHO-I NPC was less in proportion to malignant cells, usually limited to basal cells, than in other histologic types of NPC. In 10 of 11 specimens with metastases to the lymph nodes, hybridization was always limited to the malignant cells and not associated with lymphocytes. All 10 paired primary NPCs also demonstrated positive EBER1 hybridization. Only one paired specimen showed negative EBER1 in primary NPC and a metastases to a lymph node. Eight distant metastases, all EBER1-positive in their primary NPC, also demonstrated positive EBER1 hybridization signals in the malignant cells. The proportion of EBER1 positivity in metastatic NPC is higher than that in primary lesions as observed in paired specimens from the same patient.

CONCLUSIONS

Because of abundant expression of EBER1 in primary NPC as well as in metastatic malignant cells, it is recommended that EBER1 in situ hybridization be performed on routinely processed specimens whenever NPC is suspected.