Trefoil peptides, E-cadherin, and beta-catenin expression in sporadic fundic gland polyps: further evidence toward the benign nature of these lesions.

Sporadic fundic gland polyps (FGP) are the most common type of gastric polyps and their pathogenesis is still unclear, although a beta-catenin gene mutation has been described. They are regarded as benign lesions but low-grade dysplasia has been observed, arising more debate on their potential progression to a malignant phenotype. We investigated in FGP the role of factors involved in cell integrity, proliferation, and intercellular adhesion: trefoil peptides (TFF1, TFF2), MIB1, E-cadherin, and beta-catenin. We selected randomly 24 patients with FGP, 24 with normal gastric mucosa and 12 with atrophic gastritis with diffuse intestinal metaplasia (IM-gastritis), all Helicobacter pylori negative. The expression of all factors was examined by immunohistochemistry. In polyps and normal mucosa, TFF1 is expressed only in foveolar compartment whereas in IM-gastritis the signal is reduced in all the compartments. TFF2 is expressed in polyps and normal mucosa, in proliferative and basal compartment, whereas in IM-gastritis the expression is reduced or absent. E-cadherin is expressed in the entire zone: with a medium signal in normal mucosa and polyps, and weaker in IM-gastritis. The beta-catenin's signal in normal mucosa and polyps is moderate-to-intense in proliferative and basal compartments, whereas in IM-gastritis signal is significantly reduced in all the compartments. MIB1 in normal mucosa and polyps is expressed only in proliferative compartment, whereas its expression is stronger in IM-gastritis and involves also basal compartment. In conclusion all the factors considered were normally expressed in FGP and this, especially considered against the findings in IM-gastritis, supports the benign nature of FGP.

Tight junction formation in early Xenopus laevis embryos: identification and ultrastructural characterization of junctional crests and junctional vesicles.

How tight junctions (TJ) form during early amphibian embryogenesis is still an open question. We used time-lapse video microscopy, scanning electron microscopy (SEM), TEM and freeze-fracture to gain new insight into TJ biogenesis in early clevages of Xenopus laevis. Video analysis suggests three phases in junction formation between blastomeres. A first "waiting" phase, where new unpigmented lateral membranes are generated. A second "mixing" phase, where the unpigmented lateral membrane is separated from the pigmented apical membrane by an area showing a limited degree of intermingling of cortical pigment. And a third "sealing" phase, characterized by the formation of cingulin-containing boundaries between membrane domains, and their rapid directional adhesion in a zipper-like fashion. By SEM, we characterized these boundaries ("junctional crests", JC) as arrays of villiform protrusions at the border between old and new membranes. In the 2-cell embryo, JC are deeply located, and thus not visible at the surface, but they become increasingly more superficial as cleavages progress. After adjacent blastomeres have adhered to each other, fractured JC display linear arrays of junctional vesicles (JV) of 1-3 mum diameter. TEM analysis shows that JV are symmetrically located near the apposed membranes of adjacent blastomeres, and that the membranes near the JV display focal sites of intimate contact, typical of TJ. Freeze-fracture analysis confirms that intramembrane fibrils, typical of TJ, are present at adhesion sites. We conclude that TJ are formed following the sealing of JC, through the recruitment, sorting and assembly of membrane and cytoplasmic proteins at or near JV.