title: Nasal polyposis in Peutz-Jeghers syndrome: a distinct histopathological and molecular genetic entity.
abstract: BACKGROUND
  Peutz-Jeghers syndrome (PJS) is an autosomal dominant hamartomatous polyposis syndrome of the gastrointestinal tract, caused by a germline STK11/LKB1 mutation. Nasal polyposis was described in the original report by Peutz. Recently, a molecular-genetic association between nasal polyposis and PJS has been reported.
  
  
  OBJECTIVE
  To further explore the occurrence and pathogenesis of PJS-related nasal polyposis.
  
  
  METHODS
  51 patients with PJS, 84 unaffected family members and 36 spouses from 18 families with PJS were questioned for the presence of nasal polyposis. 12 PJS-related nasal polyps, 1 carcinoma of the nasal cavity and 28 sporadic nasal polyps were analysed for loss of (wild type) STK11/LKB1, eosinophilia, squamous metaplasia, dysplasia and expression of cyclo-oxygenase 2 and p53.
  
  
  RESULTS
  Nasal polyps occurred in 8 of 51 patients with PJS, and were not reported by non-affected family members (p<0.001). Germline STK11/LKB1 mutations were identified in all patients with PJS and nasal polyposis. Loss of heterozygosity was found in four of eight PJS-related nasal polyps, but not in sporadic nasal polyps (p = 0.002). PJS-related nasal polyps showed less eosinophilia than sporadic nasal polyps (p<0.001). Expression of cyclo-oxygenase 2 was found in 11 of 12 PJS-related nasal polyps and 19 of 28 sporadic nasal polyps (p>0.05). Overexpression of p53 was not found.
  
  
  CONCLUSIONS
  Nasal polyposis occurs in a significant number of Dutch patients with PJS, one of whom developed a carcinoma in the nasal cavity. The loss of heterozygosity, and the absence of eosinophilia suggest a distinct pathogenesis compared with sporadic nasal polyposis.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wendy W J
authors.initials: WW
authors.lastname: de Leng
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Westerman
authors.forename: Marian A J
authors.initials: MA
authors.lastname: Weterman
authors.forename: Marnix
authors.initials: M
authors.lastname: Jansen
authors.forename: Herman
authors.initials: H
authors.lastname: van Dekken
authors.forename: Francis M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: Felix W M
authors.initials: FW
authors.lastname: de Rooij
authors.forename: J H
authors.initials: JH
authors.lastname: Paul Wilson
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Josbert J
authors.initials: JJ
authors.lastname: Keller
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D002648:Child; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004802:Eosinophilia / Q000473:pathology; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010580:Peutz-Jeghers Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases