title: Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.
abstract: A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan. k-kikuchi@dent.meikai.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noguchi
authors.affiliation: Department of Oral Pathology, Faculty of Dentistry, Autonomous University State of México, Jesús Carranza esquina paseo Tollocan, C.P. 50130, Toluca, Mexico.
authors.forename: Michelle Wendoline Garcia-Niño
authors.initials: MW
authors.lastname: de Rivera
authors.affiliation: Second Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Hoshino
authors.affiliation: Second Division of Oral and Maxillofacial Surgery, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sakashita
authors.affiliation: Department of Pathology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Pharmacology, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka, 573-1211, Japan.
authors.forename: Tadashige
authors.initials: T
authors.lastname: Nozaki
authors.affiliation: Department of Oral Pathology, Faculty of Dentistry, Autonomous University State of México, Jesús Carranza esquina paseo Tollocan, C.P. 50130, Toluca, Mexico.
authors.forename: Blanca Silvia
authors.initials: BS
authors.lastname: González-López
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Ide
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama, 350-0283, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kusama
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D016679:Genome, Viral; D006801:Humans; D009061:Mouth Mucosa / Q000473:pathology* / Q000821:virology*; D009062:Mouth Neoplasms / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; D014764:Viral Proteins
keywords: EBV-determinated nuclear antigen-2 (EBNA-2); EBV-encoded small RNA (EBER); Epstein-Barr virus (EBV); Latent membrane protein-1 (LMP-1); Oral squamous cell carcinoma (OSCC)