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Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

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Abstract

Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.

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References

  1. Angres B, Kim L, Jung R, Gessner R, Tauber R (2001) LI-cadherin gene expression during mouse intestinal development. Dev Dyn 221:182–193

    Article  PubMed  CAS  Google Scholar 

  2. Berndorff D, Gessner R, Kreft B, Schnoy N, Lajous-Petter A, Loch N, Reutter W, Hortsch M, Tauber R (1994) Liver–intestine cadherin: molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine. J Cell Biol 125:1353–1369

    Article  PubMed  CAS  Google Scholar 

  3. Conacci-Sorrell M, Zhuringky J, Ben-Ze'ev A (2002) The cadherin-catenin adhesion system in signaling and cancer. J Clin Invest 109:987–991

    Article  PubMed  CAS  Google Scholar 

  4. Dantzig A, Hoskins J, Tabas L, Bright S, Shepard R, Jenkins I, Duckworth D, Sportsman J, Mackensen D, Paul R Jr (1994) Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science 264:430–433

    Article  PubMed  CAS  Google Scholar 

  5. Gessner R, Tauber R (2000) Intestinal cell adhesion molecules. Liver–intestine cadherin. Ann NY Acad Sci 915:136–143

    Article  PubMed  CAS  Google Scholar 

  6. Hinoi T, Lucas PC, Kuick R, Hanash S, Cho KR, Fearon ER (2002) CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithelium and intestinal metaplasia. Gastroenterology 123:1565–1577

    Article  PubMed  CAS  Google Scholar 

  7. Japanese Classification of Gastric Carcinoma, 1st English edn. Kanehara, Tokyo, pp 38–65

  8. Ko S, Chu K, Luk J, Wong B, Yuen S, Leung S, Wong J (2004) Overexpression of LI-cadherin in gastric cancer is associated with lymph node metastasis. Biochem Biophys Res Commun 319:562–568

    Article  PubMed  CAS  Google Scholar 

  9. Ko S, Chu K-M, Luk JM-C, Wong BW-Y, Yuen S-T, Leung S-Y, Wong J (2005) CDX2 co-localized with liver–intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach. J Pathol 205:615–622

    Article  PubMed  CAS  Google Scholar 

  10. Kreft B, Berndorff D, Bottinger A, Finnemann S, Wedlich D, Hortsch M, Tauber R, Gessner R (1997) LI-cadherin-mediated cell–cell adhesion does not require sytoplasmic interactions. J Cell Biol 136:1109–1121

    Article  PubMed  CAS  Google Scholar 

  11. Lauren P (1965) The two histological main types of gastric carcinoma. Diffuse and so-called intestinal type carcinoma: an attempt at histological classification. Acta Pathol Microbiol Scand 64:31–49

    PubMed  CAS  Google Scholar 

  12. Mayer B, Johnson J, Leitl F, Jauch K, Heiss M, Schildberg F, Birchmeier W, Funke I (1993) E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53:1690–1695

    PubMed  CAS  Google Scholar 

  13. Mizoshita T, Tsukamoto T, Inada K, Ogasawara N, Hirata A, Kato S, Joh T, Itoh M, Yamamura Y, Tatematsu M (2004) Immunohistochemically detectable Cdx2 is present in intestinal phenotypic elements in early gastric cancers of both differentiated and undifferentiated types, with no correlation to non-neoplastic surrounding mucosa. Pathol Int 54:392–400

    Article  PubMed  CAS  Google Scholar 

  14. Oue N, Shigeishi H, Kuniyasu H, Yokozaki H, Kuraoka K, Ito R, Yasui W (2001) Promoter hypermethylation of MGMT is associated with protein loss in gastric carcinoma. Int J Cancer 93:805–809

    Article  PubMed  CAS  Google Scholar 

  15. Silberg D, Swain G, Suh E, Traber P (2000) Cdx1 and Cdx2 expression during intestinal development. Gastroenterology 119:661–671

    Article  PubMed  Google Scholar 

  16. Sobin L, Wittekind C (1997) TNM classification of malignant tumors, 5th edn. Wiley-Liss, New York, pp 59–62

    Google Scholar 

  17. Takamura M, Sakamoto M, Ino Y, Shimamura T, Ichida T, Asakura H, Hirohashi S (2003) Expression of liver–intestine cadherin and its possible interaction with galectin-3 in ductal adenocarcinoma of the pancreas. Cancer Sci 94:425–430

    Article  PubMed  CAS  Google Scholar 

  18. Wong BW, Luk JM, Ng IO, Hu MY, Liu KD, Fan ST (2003) Identification of liver-intestine cadherin in hepatocellular carcinoma—a potential disease marker. Biochem Biophys Res Commun 311:618–624

    Article  PubMed  CAS  Google Scholar 

  19. Yasui W, Sano T, Nishimura K, Kitadai Y, Ji ZQ, Yokozaki H, Ito H, Tahara E (1993) Expression of P-cadherin in gastric carcinomas and its reduction in tumor progression. Int J Cancer 54:49–52

    Article  PubMed  CAS  Google Scholar 

  20. Yasui W, Oue N, Ito R, Kuraoka K, Nakayama H (2004) Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implication. Cancer Sci 95:385–392

    Article  PubMed  CAS  Google Scholar 

  21. Yuasa Y, Nagasaki H, Akiyama Y, Sakai H, Nakajima T, Ohkura Y, Takizawa T, Koike M, Tani M, Iwai T, Sugihara K, Imai K, Nakachi K (2005) Relationship between Cdx2 gene methylation aid dietary factors in gastric cancer patients. Carcinogenesis 26:193–200

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, and Technology of Japan, and the Ministry of Health, Labor, and Welfare of Japan. The authors thank Masayoshi Takatani and Mutsumi Ueda for their skillful technical assistance.

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Authors and Affiliations

  1. Department of Radiobiology/Molecular Epidemiology, Radiation Effect Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima, Japan

    Reiko Ito & Kei Nakachi

  2. Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan

    Naohide Oue, Kyoko Kunimitsu, Hirofumi Nakayama & Wataru Yasui

  3. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Kazuhiro Yoshida

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  1. Reiko Ito
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  2. Naohide Oue
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  3. Kazuhiro Yoshida
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  4. Kyoko Kunimitsu
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  5. Hirofumi Nakayama
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  6. Kei Nakachi
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  7. Wataru Yasui
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Correspondence to Wataru Yasui.

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Ito, R., Oue, N., Yoshida, K. et al. Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer. Virchows Arch 447, 717–722 (2005). https://doi.org/10.1007/s00428-005-0015-2

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  • DOI: https://doi.org/10.1007/s00428-005-0015-2

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