Nasal polyposis in Peutz-Jeghers syndrome: a distinct histopathological and molecular genetic entity.
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.
de Leng
Wendy W J
WW
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Westerman
Anne Marie
AM
Weterman
Marian A J
MA
Jansen
Marnix
M
van Dekken
Herman
H
Giardiello
Francis M
FM
de Rooij
Felix W M
FW
Paul Wilson
J H
JH
Offerhaus
G Johan A
GJ
Keller
Josbert J
JJ
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
D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases