Purpose: EBV has been associated with nasopharyngeal carcinomas (NPC). In North Africa, the incidence is bimodalöthe first peak occurring at f20 years of age and the second peak occurring at f50 years. Standard diagnostic tests based on immunofluorescence using anti-IgA EBV have shown that young North African patients have a negative serology compared with older patients.We are interested in two EBV-encoded oncoproteins, LMP1and BARF1, which have thus far not been studied in terms of their potential as diagnostic markers for NPC. These two viral oncoproteins have been detected in cell culture media, so we tested whether they could be detected in the serum and saliva of patients with NPC. Experimental Design: LMP1 and BARF1 proteins were analyzed in the sera and saliva of young patients and adult patients with NPC from North Africa and China. We then examined whether the secreted proteins had biological activity by analyzing their mitogenic activity. Results: Both LMP1 and BARF1 were present in the serum and saliva from North African and Chinese patients with NPC. All young North African patients secreted both proteins, whereas 62% and 100% of adult patients secreted LMP1 and BARF1, respectively. From animal studies, the secreted LMP1was associated with exosome-like vesicles. These secreted EBV oncoproteins showed a powerful mitogenic activity in B cells. Conclusion: Both proteins will be a good diagnostic marker for NPC whereas BARF1is a particularly promising marker for all ages of patients with NPC. Their mitogenic activity suggests their implication in the oncogenic development of NPC.
Nasopharyngeal carcinoma (NPC) is a human malignancyderived from the epithelium of the nasopharyngeal cavity. It is one of the most striking examples of a human malignancy that is consistently associated with a virus (1 -3). The EBV genome is contained in all malignant NPC cells and it encodes viral proteins that contribute to the malignant phenotype (4 -6). Even though infection with EBV is ubiquitous in humans, the incidence of NPC is extremely variable, depending on the geographic area. Whereas the incidence of NPCs in the Chinese population peaks at f50 years of age, there are two peaks of incidence in North Africa-one at f20 years of age and the second at f50 years of age (6). Because of the close association of EBV with NPC, detection of EBV anti-IgA, anti-EA, or anti-VCA by immunofluorescence tests in serum from patients with NPC is used in most Asian countries. However, this test is almost always negative for young North African patients (6). Recent data showed a successful diagnosis of NPC by molecular serology based on EBV-encoded proteins, DNase, thymidine kinase, and p16 VCA used as viral antigens (7 -10). Virus load in patient blood has been used as a diagnostic marker for NPC (11,12), but high levels have been reported in nonneoplastic disorders, gastrointestinal malignancies, and for lymphoproliferative disease (13,14). We therefore need a more reliable, simpler, and specific diagnostic test for NPC.Seve...