title: Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma.
abstract: The expression of E-cadherin located in the adherens junction varies with disruption of glandular morphology and loss of differentiation. It has been suggested that the loss of tight junction function is related to tumor differentiation, but little is known about the roles of major proteins, such as claudin 4 and ZO-1, in gastric cancer. The aims of this study were to examine the differences in expression of E-cadherin, claudin 4, and ZO-1 proteins according to the pathological and clinical features of advanced gastric cancer. The expression of E-cadherin, claudin 4, and ZO-1 was analyzed immuno-histochemically using formalin-fixed, paraffin-embedded tissues obtained from 49 patients who underwent radical resection for advanced gastric cancer. Western blot analysis and RT-PCR were performed in representative tumors of the diffuse or intestinal type. Immunostaining for E-cadherin, claudin 4, and ZO-1 was reduced in 69, 69, and 37% of cancers, respectively. Similar patterns of expression were noted for E-cadherin and claudin 4, but ZO-1 expression differed. According to the Lauren classification, the reduced expression of E-cadherin and claudin 4 was more frequent in diffuse than intestinal type tumors (p<0.001). The reduced expression of E-cadherin and claudin 4 correlated with poor differentiation (p<0.05). Western blot analysis and RT-PCR also showed decreased claudin 4 expression in diffuse type tumors and poorly-differentiated adenocarcinoma. The reduced expression of claudin 4 and E-cadherin correlates with disruption of glandular structure and loss of differentiation, which suggests that the dysfunction of claudin 4 may play a role in the disruption of cell-to-cell adhesion in diffuse type gastric cancer and in a loss of differentiation.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kyunghee University College of Medicine, South Korea.
authors.forename: Sang Kil
authors.initials: SK
authors.lastname: Lee
authors.forename: Jung
authors.initials: J
authors.lastname: Moon
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
authors.forename: Jae Bock
authors.initials: JB
authors.lastname: Chung
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis; D002454:Cell Differentiation; D062506:Claudin-4; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: C568157:CLDN4 protein, human; D015820:Cadherins; D062506:Claudin-4; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein