Pathology of the Gastrointestinal Tract

2017 Edition
| Editors: Fátima Carneiro, Paula Chaves, Arzu Ensari

E-Cadherin, Hereditary Diffuse Gastric Cancer

  • Chella R. S. van der PostEmail author
  • Fátima Carneiro
Reference work entry


HDGC; Hereditary diffuse gastric carcinoma


E-cadherin gastric carcinoma or hereditary diffuse gastric carcinoma (HDGC) is a form of gastric cancer in patients with germline alterations in the CDH1 gene. HDGC is an autosomal-dominant cancer-susceptibility syndrome and is characterized by diffuse gastric cancer and lobular breast cancer. In 1998, Guildford et al. identified germline mutations in the CDH1 gene to be the cause of HDGC by linkage analysis and mutation screening in three Maori kindreds with multigenerational gastric cancer in New Zealand.

CDH1 encodes the protein E-cadherin, which plays an important role in cell polarity and the maintenance of epithelial integrity. Due to mutations in CDH1, the cell-cell adhesion mediated by E-cadherin is lost, which causes disruption of the correct spatial organization of the cells. This interferes with processes that regulate cell division, such as the orientation of the mitotic spindle. Abrogated cell polarity may...

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References and Further Reading

  1. Carneiro, F., Huntsman, D. G., Smyrk, T. C., Owen, D. A., Seruca, R., Pharoah, P., et al. (2004). Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening. The Journal of Pathology, 203(2), 681–687.CrossRefGoogle Scholar
  2. Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., et al. (1998). E-cadherin germline mutations in familial gastric cancer. Nature, 392(6674), 402–405.CrossRefGoogle Scholar
  3. Guilford, P., Humar, B., & Blair, V. (2010). Hereditary diffuse gastric cancer: Translation of CDH1 germline mutations into clinical practice. Gastric Cancer, 13(1), 1–10.CrossRefGoogle Scholar
  4. Hansford, S., Kaurah, P., Li-Chang, H., et al. (2015). Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncology.Google Scholar
  5. Majewski, I. J., Kluijt, I., Cats, A., Scerri, T. S., de Jong, D., Kluin, R. J., et al. (2013). An α-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer. The Journal of Pathology, 229(4), 621–629.CrossRefGoogle Scholar
  6. Oliveira, C., Sousa, S., Pinheiro, H., Karam, R., Bordeira-Carrico, R., Senz, J., et al. (2009). Quantification of epigenetic and genetic 2nd hits in CDH1 during hereditary diffuse gastric cancer syndrome progression. Gastroenterology, 136(7), 2137–2148.CrossRefGoogle Scholar
  7. van der Post, R. S., Vogelaar, I. P., Carneiro, F., et al. (2015). Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. Journal of medical genetics. 52(6), 361–374.Google Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Chella R. S. van der Post
    • 1
    Email author
  • Fátima Carneiro
    • 2
  1. 1.Department of PathologyRadboud University Medical CenterNijmegenThe Netherlands
  2. 2.Faculty of Medicine of Porto University, Centro Hospitalar São João and Ipatimup/i3SPortoPortugal