title: Epstein-Barr virus-associated gastric carcinoma: a distinct carcinoma of gastric phenotype by claudin expression profiling.
abstract: Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) is a distinct subtype with characteristic clinicopathological features. To better characterize its cellular characteristics, 43 cases of EBV-associated GC, 68 cases of EBV-negative GC, and non-neoplastic gastric mucosa in adults and fetuses were examined immunohistochemically. We quantified the expression of the major tight-junction protein claudin (CLDN) -1, -3, -4, -7, and -18 together with gastric mucins (MUC5AC and MUC6), intestinal mucin (MUC2), and CD10. EBV-associated GC showed a high frequency of CLDN18 expression (84%) and a low frequency of CLDN3 expression (5%). This expression profile corresponded to that of normal gastric epithelium in adults and fetuses. Almost half of the EBV-associated GC cases demonstrated gastric mucin expression, whereas the other half lacked mucin or CD10 expression. In contrast, as demonstrated by the expression profiles of CLDN3 and CLDN18, EBV-negative GC comprised a heterogeneous group of four different CLDN phenotypes: gastric, intestinal, mixed, and an undifferentiated type with variable expression patterns of mucins. These results indicate that EBV-associated GC is considerably homogenous with regard to cellular differentiation and that it preserves well the nature of the cells of origin. EBV-associated GC may undergo distinct carcinogenic processes, which differ from those of EBV-negative GC.
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Shinozaki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ushiku
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.forename: Rumi
authors.initials: R
authors.lastname: Hino
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakatani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D005333:Fetus / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009077:Mucins / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D010641:Phenotype; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019108:Tight Junctions / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009077:Mucins