The expression of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue.
BACKGROUND
The claudins (CLDNs) are a family of functional tight junction proteins, and are involved with the epithelial-to-mesenchymal transition (EMT). The claudin proteins have a significant influence on the biological behavior of tumor progression in several types of cancers. In this study, we aimed to evaluate the expression pattern of claudin-1, claudin-2, claudin-3, and claudin-4 in gastric cancer tissue.


METHODS
Tissue was obtained from surgically resected specimens of 72 patients who were diagnosed with gastric adenocarcinoma at a single institution. The expressions of claudin-1, claudin-2, claudin-3, and claudin-4 were determined by immunohistochemical staining with the ABC method.


RESULTS
Claudin-2 demonstrated the highest expression rate (73.6%) and claudin-4 demonstrated the lowest expression rate (44.4%). The expression of claudin-1 was significantly lower in cases of intestinal type adenocarcinoma based on the Lauren classification. The expressions of claudin-3 and claudin-4 were significantly lower in cases with positive lymphatic invasion. The expression of claudin-3 was significantly lower in cases with an advanced T-stage (T3 and T4). The expression of claudin-3 showed significantly positive correlations with the expression of the other claudin proteins. In survival analysis, the expression of claudin-4 was related to good overall survival rate with significance (P = 0.046).


CONCLUSIONS
We suggest that claudin-3 and claudin-4 represent useful molecular markers for gastric cancer. Claudin-3 and claudin-4 would be the most important proteins related to the lymphatic invasion process, and claudin-4 would be useful with prognostic marker based on our results. Further investigations with a greater number of subjects are required to identify the action mechanism of claudin in gastric cancer.
Jung
Hun
H
Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Jun
Kyong Hwa
KH
Jung
Ji Han
JH
Chin
Hyung Min
HM
Park
Woo Bae
WB
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C491875:CLDN2 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D057167:Claudins; D008565:Membrane Proteins