Impaired gastric gland differentiation in Peutz-Jeghers Syndrome

A52

Gastrointestinal polyps in the Peutz-Jeghers cancer predisposition syndrome and its mouse model contain a characteristic smooth muscle enriched mesenchyme covered by an apparently well differentiated epithelium. This study aimed to explore Peutz-Jeghers polyp formation through characterizing the epithelium of polyps and predisposed mucosa in the stomach.
 >Different types of cells were identified in tissue sections from Lkb1^+/- mice and Peutz-Jeghers patients using Periodic acid- Schiff- Alcian blue stain, Grissinia Simplicifolia lectin, and antibodies against pepsinogen C, gastrin, Ki-67, desmin, lysozyme and smooth muscle alpha-actin.
 >Pepsinogen C expressing gland cells (mucopeptic and chief cells), as well as parietal cells, were strongly reduced or completely absent in large gastric Peutz-Jeghers polyps. Incipient mouse polyps also expressed less pepsinogen C and the unaffected mucosa of young Lkb1^+/- animals had an increased number of pepsinogen C negative glands (25%; P = 0,045). Neck cells, precursors to mucopeptic and chief cells, were increased in polyp epithelium lining smooth muscle marker expressing mesenchyme. The epithelium of small intestinal Peutz-Jeghers polyps also lacked differentiated gland cells (Paneth cells).
 >The shift in epithelial homeostasis towards undifferentiated cells progressing from unaffected predisposedmucosa to incipient polyps to large polyps suggests a causative role for disrupted neck-to-mucopeptic cell transition in gastric Peutz-Jeghers polyp formation. Similar differentiation blocks are likely to occur during polyp formation also in other affected organs, like intestine. The aberrant epithelium in Peutz-Jeghers patient polyps argues that they harbor an increased susceptibility to neoplasia.