N.V. Danilova – Ph.D. (Med.), Senior Research Scientist, Department of Pathology, Medical Research  and Educational Center, Lomonosov Moscow State University

E-mail: natalyadanilova@gmail.com

K.A. Anikina – Student, Faculty of Fundamental Medicine, Lomonosov Moscow State University E-mail: christinanikina@gmail.com

N.A. Oleynikova – Ph.D. (Med.), Research Scientist, Department of Pathology, Medical Research and Educational Center, Lomonosov Moscow State University E-mail: noleynikova@mc.msu.ru

Claudin-4 is a member of a large family of transmembrane proteins which are essential for the formation and function of tight junctions. Aberrant expression of claudin proteins potentially leads to structural and functional damage of tight junctions and may promote tumorigenesis and cancer progression.

Several studies have revealed altered claudin-4 expression in gastric cancer. Claudin-4 expression is significantly higher in welldifferentiated carcinoma than in poorly differentiated carcinoma which shows lower expression. Claudin-4 level is associated with the histological type according to Lauren classification. The expression of claudin-4 is significantly higher in intestinal-type gastric cancer in comparison to the diffuse-type. Reduced claudin-4 expression in primary tumors is associated with the presence of distant metastass. Overall survival in patients with low claudin-4 expression is significantly shorter than in patients with high expression. Increased claudin-4 expression is related to good prognosis in 4-year overall survival results. There are conflicting results regarding the association between claudin-4 expression in gasric cancer and T stage, N stage, lymphatic invasion.

The aim of this study was to evaluate the expression of claudin-4 in gasric adenocarcinoma and in adjacent normal mucosa and its association with clinicopathological parameters. A total of 69 tissue specimens from patients with gastric cancer were obtained. Immunohistochemistry was performed using mouse polyclonal antibodies to claudin-4. The expression of claudin-4 was observed in 69 (100%) gastric cancer samples; 67 of these cases showed strong claudin-4 staining and 2 demonstrated moderate staining. Claudin-4 staining was observed in 45 (65,2%) of adjacent normal mucosa samples. Among all samples, 30 showed strong claudin-4 staining, 8 were characterised by a moderate staining, whereas 7 showed a weak staining. In 24 (34,8%) samples claudin-4 expression was not observed. A significant difference was found in the expression levels of claudin-4 between gastric cancer and adjacent normal mucosa (p<0,05). The expression of claudin-4 was increased in 38 (55,1%) tumors; 31 (44,9%) tumors showed no elevation of claudin-4 level compared to adjacent normal mucosa. There were no significant association between claudin-4 expression in gasric cancer and with clinicopathological parameters, although we found that high expression of claudin-4 in gastric cancer may be associated with large tumor size. Thus, claudin-4 may have potential to be used as a prognostic marker in gastric cancer.

Danilova N.V., Anikina K.A., Oleynikova N.A. Claudin-4 expression in gastric adenocarcinoma cells. Technologies of living systems. 2020. V. 17. № 3. P. 46–DOI: 10.18127/j20700997-202003-05 (In Russian).

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