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β-Catenin activation in fundic gland polyps, gastric cancer and colonic polyps in families afflicted by ‘gastric adenocarcinoma and proximal polyposis of the stomach’ (GAPPS)
  1. Lucas A McDuffie1,
  2. Arvind Sabesan1,
  3. Michael Allgäeuer2,
  4. Liqiang Xin2,
  5. Christopher Koh3,
  6. Theo Heller3,
  7. Jeremy L Davis1,
  8. Mark Raffeld2,
  9. Markku Miettienen2,
  10. Martha Quezado2,
  11. Udo Rudloff1
  1. 1Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  3. 3Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Dr Udo Rudloff, Thoracic and Gastrointestinal Oncology Branch, Gastrointestinal Oncology Section, Investigator, Center for Cancer Research, National Cancer Institute, Building 10—Hatfield CRC, Room 4-5950, Bethesda, MD 20892, USA; rudloffu{at}mail.nih.gov

Abstract

Aim To evaluate possible colon involvement in the ‘gastric adenocarcinoma and proximal polyposis of the stomach’ (GAPPS) gastrointestinal polyposis syndrome.

Methods Prospective clinicopathological evaluation of two GAPPS families and expression of nuclear β-catenin, p53 and Ki67 measured by immunohistochemistry on endoscopic and surgical specimens from patients with GAPPS.

Results Patients with the GAPPS phenotype were more frequently affected by colonic polyps than patients at risk within the same families (p<0.01). Colonic polyps shared immunohistochemical features of fundic gland polyps and gastric cancers including increased expression of nuclear β-catenin, Ki67 and p53. Both gastric and colonic lesions harboured activating somatic variants of β-catenin signalling.

Conclusions Similarities in expression markers in fundic gland and colonic polyps, together with an enrichment of colonic adenomas in family members affected by GAPPS phenotype compared with family members at risk, support mild colonic involvement of this rare cancer syndrome. Colonoscopic screening might be warranted.

Clinical Trial Registration Number #09-C-0079; Results.

  • GASTRIC CANCER
  • GASTRIC PATHOLOGY
  • FAMILIAL CANCERS

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