Study of claudin-4 in the diagnosis and treatment of endometrial carcinoma

Abstract

To clarify the role of claudin-4 in endometrial tumorigenesis and explore claudin-4 be as potentially useful agent in the treatment of endometrial carcinoma. The expression of claudin-4 in 62 endometrioid endometrial carcinoma (EEC), 30 atypical hyperplasia endometrial tissue and 60 human normal endometrium was determined using immunohistochemistry and real-time PCR. Ninety female BALB/c mice were transplanted with Ishikawa endometrial cancer cells, which were divided into three groups with different intraperitoneal treatments with cisplatin, paclitaxel and saline solution. After the observation period, the tumors were extracted and stained with monoclonal antibody against claudin-4. The messenger RNA expression of claudin-4 was also detected using real-time PCR. Among the EEC samples, 34% (21/62) showed medium staining for claudin-4 and 66% (41/62) showed intense staining. In atypical hyperplasia group, 27% (8/30) showed weak staining, 53% (16/30) showed medium staining and 20% (6/30) showed intense staining for claudin-4. Of the normal endometrial tissue, 47% (28/60) showed weak staining and 53% (32/60) showed no staining for claudin-4. According to real-time PCR, the relative quantity of claudin-4 was 170 ± 12 in EEC group, 89 ± 15 in atypical hyperplasia group and 18 ± 3 in normal endometrium. Compared with those in atypical hyperplasia group and normal endometrium group, the protein and mRNA expression of claudin-4 were significantly increased in the group of EEC (all P < 0.05). In the study of Ishikawa xenografts, no significant changes in tumor volume and claudin-4 expression were shown in paclitaxel group compared with that in the control group. Nevertheless, a significant reduction of the tumor growth and a significant decrease in claudin-4 expression were observed in cisplatin group. After cisplatin treatment, the tumor volume was significantly decreased [(0.51 ± 0.21) versus (0.73 ± 0.12) cm(3)], and the mRNA expression of claudin-4 was also significantly decreased (153 ± 35 versus 273 ± 27). These results demonstrate that claudin-4 is strongly expressed in EEC, which may be a useful biomarker to monitor the effects of chemotherapy in patients with endometrial carcinoma.