Studies have revealed that Epstein-Barr virus (
EBV) infection, genetic aberration, and environmental factors are of importance in the development of
nasopharyngeal carcinoma (NPC), although the definite mechanism remains to be fully elucidated. The aim of our study is to investigate using tissue microarray analysis whether differential expression of
EBV-encoded small RNA-1 (EBER-1) and several
tumor-related genes were associated with NPC
carcinogenesis. Immunohistochemistry and in situ hybridization were performed on tissue microarrays containing 148 NPCs and 164 noncancerous nasopharyngeal epithelia (NPE) with different morphologic features. We found that overexpressions of
EBER-1 hybridization signals, p53, p21ras, and bcl-2
proteins and loss expressions of p16 and p27
proteins were significantly increased in NPC tissues compared with normal NPE and hyperplastic NPE (P </= .001). The overexpressions of
EBER-1 and p53 (P < .001) and the loss expressions of P16 (P < .001) and P27 (P = .005) were also significantly higher and more frequently observed in NPC than in dysplastic NPE. The positive expression of
EBER-1 hybridization signals in NPC had significant associations with overexpressions of p53 (P < .001), p21ras (P = .041), and bcl-2
proteins (P < .001) and loss expression of p16
protein (P = .001). Further analysis confirmed that the abnormal expression of p53, p16, and p27
proteins occurred in the earliest stage of nasopharyngeal epithelial
carcinogenesis. In the final logistic regression analysis model, the positive hybridization signals of
EBER-1 and the abnormal expression of p53, p16, and p27
proteins were independent contributions for nasopharyngeal
carcinogenesis, and
EBER-1 was the most significant, independent predictor of nasopharyngeal
carcinogenesis (hazard ratio = 13.412, 95% confidence interval 6.179-29.111, P < .001). In conclusion,
EBV infection, together with overexpressions of p53, and loss expressions of p16 and p27
proteins are involved in the multistep process of human nasopharyngeal epithelial
carcinogenesis.