Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening

Fátima Carneiro, David G. Huntsman, Thomas C. Smyrk, David A. Owen, Raquel Seruca, Paul Pharoah, Carlos Caldas, Manuel Sobrinho-Simões

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome caused, in 30-40% of cases, by germline mutations of the E-cadherin/CDH1 gene. The presence of clinically undetectable early gastric cancers has been previously reported in ten of ten prophylactic gastrectomies from germline E-cadherin mutation carriers. In the present study, detailed maps of the distribution of invasive cancers in nine of these ten stomachs were produced and precursor lesions of HDGC searched for. The nine gastrectomy specimens contained from 1 to 161 foci of early diffuse gastric cancer, occupying 0.005-2.96% of the gastric mucosa. Seven specimens contained focal in situ signet ring carcinoma. Pagetoid spread of signet ring cells was observed beneath the epithelial lining of gastric foveolae/glands. Helicobacter pylori organisms and associated pathology were absent from all cases. Two-dimensional maps of the gastrectomy specimens revealed lesions throughout the gastric mucosa without evidence of antral clustering. The distribution and size of the cancers in the gastrectomy specimens indicate that standard endoscopic screening with random or geographically targeted biopsies is unlikely to provide sufficiently sensitive clinical screening for at-risk individuals. An in situ precursor of signet ring carcinoma was identified and a model for neoplastic progression in the setting of HDGC is proposed.

Original languageEnglish (US)
Pages (from-to)681-687
Number of pages7
JournalJournal of Pathology
Volume203
Issue number2
DOIs
StatePublished - Jun 1 2004

Keywords

  • E-cadherin
  • Germline mutations
  • Hereditary gastric cancer
  • Pagetoid spread
  • Screening

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Carneiro, F., Huntsman, D. G., Smyrk, T. C., Owen, D. A., Seruca, R., Pharoah, P., Caldas, C., & Sobrinho-Simões, M. (2004). Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening. Journal of Pathology, 203(2), 681-687. https://doi.org/10.1002/path.1564