title: Differential expression of Epstein-Barr virus-encoded RNA and several tumor-related genes in various types of nasopharyngeal epithelial lesions and nasopharyngeal carcinoma using tissue microarray analysis.
abstract: 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.
authors.affiliation: Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan, China; Department of Pathology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Song-Qing
authors.initials: SQ
authors.lastname: Fan
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Bing-Yi
authors.initials: BY
authors.lastname: Xiao
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Tan
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Li
authors.forename: Shou-Rong
authors.initials: SR
authors.lastname: Shen
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Zhang
authors.forename: Yang-Jue
authors.initials: YJ
authors.lastname: Ou
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhuo
authors.forename: Songquing
authors.initials: S
authors.lastname: Fan
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Zhou
authors.forename: Gui-Yuan
authors.initials: GY
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000032:analysis*; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; C099537:Epstein-Barr virus encoded RNA 1; D009363:Neoplasm Proteins; D012367:RNA, Viral