Mucosal prolapse in the pathogenesis of Peutz-Jeghers polyposis (original) (raw)

Mucosal prolapse in the pathogenesis of Peutz-Jeghers polyposis

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  1. M Jansen1,
  2. W W J de Leng1,
  3. A F Baas2,
  4. H Myoshi3,
  5. L Mathus-Vliegen1,
  6. M M Taketo3,
  7. H Clevers2,
  8. F M Giardiello4,
  9. G J A Offerhaus1
  10. 1Departments of Pathology and Gastroenterology, Academic Medical Centre, Amsterdam, the Netherlands
  11. 2Hubrecht Laboratory, Centre for Biomedical Genetics, Utrecht, the Netherlands
  12. 3Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  13. 4Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
  14. Correspondence to:
    Dr G J A Offerhaus
    Academic Medical Centre of the University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; g.j.offerhaus{at}amc.uva.nl

Abstract

Germline mutations in LKB1 cause the rare cancer prone disorder Peutz-Jeghers syndrome (PJS). Gastrointestinal hamartomatous polyps constitute the major phenotypic trait in PJS. Hamartomatous polyps arising in PJS patients are generally considered to lack premalignant potential although rare neoplastic changes in these polyps and an increased gastrointestinal cancer risk in PJS are well documented. These conflicting observations are resolved in the current hypothesis by providing a unifying explanation for these contrasting features of PJS polyposis. We postulate that a genetic predisposition to epithelial prolapse underlies the formation of the polyps associated with PJS. Conventional sporadic adenomas arising in PJS patients will similarly show mucosal prolapse and carry the associated histological features.

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