Epstein-Barr virus-associated gastric carcinoma: a distinct carcinoma of gastric phenotype by claudin expression profiling.
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.
Shinozaki
Aya
A
Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ushiku
Tetsuo
T
Morikawa
Teppei
T
Hino
Rumi
R
Sakatani
Takashi
T
Uozaki
Hiroshi
H
Fukayama
Masashi
M
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*
D008565:Membrane Proteins; D009077:Mucins