Originally published as JHC exPRESS on April 27, 2009. doi:10.1369/jhc.2009.953810
Volume 57 (8): 775-785, 2009 Copyright ©The Histochemical Society, Inc. Epstein-Barr Virus–associated Gastric Carcinoma: A Distinct Carcinoma of Gastric Phenotype by Claudin Expression Profiling
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo Japan Correspondence to: Masashi Fukayama, MD, Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: mfukayama-tky{at}umin.ac.jp 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. (J Histochem Cytochem 57:775–785, 2009)
Key Words: Epstein-Barr virus gastric carcinoma immunohistochemistry claudin mucin
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