Overexpression of epidermal growth factor receptor in Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is characterized bygastrointestinal hamartomatous polyposis, mucocutaneouspigmentation, and a predisposition to cancer. Theetiology of this syndrome is unknown. We investigated the expression of epidermal growth factorreceptor (EGFr), transforming growth factor-α(TGF-α), transforming growthfactor-β1 (TGF-β1) andtransforming growth factor-β receptor (TGF-β RII) between normal and Peutz-Jeghers smallbowel tissues. In addition, immunoprecipitation byphosphotyrosine antibodies followed by EGFr westernblotting was measured and compared between aPeutz-Jeghers hamartoma and normal duodenal tissue. EGFrexpression was increased 2.5-fold in normal andhamartomatous tissue of Peutz-Jeghers patients comparedto normal small bowel tissue. In Peutz-Jeghers tissues, the major EGFr immunoreactive band wasincreased size from 170 to approximately 200 kDa. Usingan antibody specific for activated EGFr, this largersize band was predominant in Peutz-Jeghers tissue.Immunoprecipitation of a hamartoma by a phosphotyrosine specificantibody followed by western blotting for EGFrdemonstrated this 200-kDa band. Expression ofTGF-α, TGF-β1, TGF-β RII wasnot significantly different between normal and Peutz-Jeghers tissues. Inconclusion, EGFr was overexpressed in normal andhamartomatous small bowel tissue of Peutz-Jegherspatients, which suggests that EGFr in Peutz-Jegherstissue is persistently activated or highly stimulatedby endogenous ligands and also suggests a possible rolefor EGFr in the pathogenesis of Peutz-Jeghers syndrome.