Overexpression of epidermal growth factor receptor in Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is characterized by gastrointestinal hamartomatous polyposis, mucocutaneous pigmentation, and a predisposition to cancer. The etiology of this syndrome is unknown. We investigated the expression of epidermal growth factor receptor (EGFr), transforming growth factor-α (TGF-α), transforming growth factor-β₂ (TGF-β₁) and transforming growth factor-β receptor (TGF-β RII) between normal and Peutz- Jeghers small bowel tissues. In addition, immunoprecipitation by phosphotyrosine antibodies followed by EGFr western blotting was measured and compared between a Peutz-Jeghers hamartoma and normal duodenal tissue. EGFr expression was increased 2.5-fold in normal and hamartomatous tissue of Peutz-Jeghers patients compared to normal small bowel tissue. In Peutz- Jeghers tissues, the major EGFr immunoreactive band was increased size from 170 to approximately 200 kDa. Using an antibody specific for activated EGFr, this larger size band was predominant in Peutz-Jeghers tissue. Immunoprecipitation of a hamartoma by a phosphotyrosine specific antibody followed by western blotting for EGFr demonstrated this 200-kDa band. Expression of TGF-α, TGF-β1, TGF-β RII was not significantly different between normal and Peutz-Jeghers tissues. In conclusion, EGFr was overexpressed in normal and hamartomatous small bowel tissue of Peutz- Jeghers patients, which suggests that EGFr in Peutz-Jeghers tissue is persistently activated or highly stimulated by endogenous ligands and also suggests a possible role for EGFr in the pathogenesis of Peutz-Jeghers syndrome.