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Originally published as JHC exPRESS on April 27, 2009.
doi:10.1369/jhc.2009.953810
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Journal of Histochemistry and Cytochemistry
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

Aya Shinozaki, Tetsuo Ushiku, Teppei Morikawa, Rumi Hino, Takashi Sakatani, Hiroshi Uozaki and Masashi Fukayama

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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