UNDIFFERENTIATED, NONKERATINIZING, AND SQUAMOUS-CELL CARCINOMA OF THENASOPHARYNX - VARIANTS OF EPSTEIN-BARR VIRUS-INFECTED NEOPLASIA

Nasopharyngeal carcinoma (NPC) samples of distinct histological types, including squamous cell carcinoma (WHO type 1), nonkeratinizing carci noma (WHO type 2), and undifferentiated carcinoma (WHO type 3), were a nalyzed for Epstein-Barr virus (EBV) infection and gene expression by using in situ and biochemical techniques. The EBV-encoded RNAs (EBER) were detected in situ in most tumor cells of all three WHO types of NP C. In foci of squamous differentiation and keratinization within less differentiated NPC and throughout the expanse of well differentiated s quamous cell carcinoma, EBER expression was less abundant. Latent memb rane protein, an EBV-encoded membrane protein, was detected in 72% (36 /50) of all NPC and 67% (6/9) of the cases of squamous cell carcinoma. The EBV genomes were present as clonal episomal forms, without detect able linear viral DNA, in all cases of squamous cell carcinoma analyze d Polymerase chain reaction amplification of cDNA detected EBV transcr iption for Epstein-Barr nuclear antigen 1, latent membrane proteins 1 and 2, and BamHI A in all samples, indicating that all forms of NPC ex press the same EBV genes. These results reveal that EBER expression is significantly decreased in areas with squamous differentiation and co nfirm that all types of NPC, regardless of histological type or differ entiation contain clonal episomal EBV genomes, express specific EBV ge nes, and are a clonal expansion of EBV-infected cells.