Immunohistological evidence for Wnt-signaling activation in Peutz-Jeghers polyposis.
OBJECTIVE
Molecular pathogenesis of gastrointestinal polyposis in Peutz-Jegher's syndrome (PJS) has been linked to the loss-of-function mutation of LKB1. Recent functional genetic studies have pointed out that LKB1 plays a physiological role in controlling the Wnt-signaling pathway and activation of the pathway as a consequence of LKB1 haploinsufficiency might be responsible for the development of harmatomatous polyps. This study aimed to look for immunohistochemical evidence of Wnt-signaling activation in PJS polyps.


METHODS
Beta-catenin immunohistochemistry patterns were evaluated in gastrointestinal polyps from five cases of PJS. All patients were also evaluated for germline mutations of LKB1 and somatic mutations of beta-catenin in the polyps.


RESULTS
Four of the five cases had germline mutations of LKB1, including two novel mutations, a one-base insertion at codon 53 and a large deletion encompassing exon 3 (codon 136-155). PJS polyps from all patients showed generalized membrane and cytoplasmic localizations of beta-catenin along the mucosal endothelium. Polyps from two cases with LKB1 mutations revealed moderate-intensity nuclear staining in approximately 20 and 70% of the polyps.


CONCLUSIONS
The study offers additional evidence of Wnt-signaling activation in PJS polyp development at the tissue level, although the degree of up-regulation was not as high as has been found in Wnt-associated neoplasms.
Chaiyapan
Walawee
W
Tumor Biology Research Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
Sangkhathat
Surasak
S
Kanngurn
Samornmas
S
Phukaoloun
Monlika
M
Chiengkriwate
Piyawan
P
Patrapinyokul
Sakda
S
D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007223:Infant; D008297:Male; D010580:Peutz-Jeghers Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D004273:DNA, Neoplasm; D051176:beta Catenin; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases