Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma

OBJECTIVE: The expression of claudins, the main tight junction proteins involved in cell adhesion and carcinogenesis, was studied in endometrioid (type I) and seropapillary (type II) endometrial adenocarcinoma. The characteristics and possible diagnostic potential of claudin expression pattern were investigated in the two cancer types having different prognosis. METHODS: Protein and mRNA expression of claudins was evaluated in 17 endometrioid carcinomas and 15 seropapillary adenocarcinomas by immunohistochemistry and real-time PCR in comparison with 38 cases of hyperplasia, normal proliferative and secretory endometrium samples. Further, protein expressions used in diagnostics (estrogen and progesterone receptors, p53, PCNA and beta-catenin) were also studied. RESULTS: In endometrioid carcinoma and hyperplasia low claudin 1 and high claudin 2 protein contents, whereas in seropapillary adenocarcinoma high claudin 1 and low claudin 2 levels were detected. Intense protein expression was noted for claudins 3, 4, 5, and 7, without significantly different patterns in carcinoma, hyperplasia, secretory, and proliferative endometrium. Real-time PCR results confirmed differences in claudin 1 but not claudin 2 mRNA expression, whereas some minor discrepancies were observed in comparison with immunohistochemistry patterns. CONCLUSION: The two types of endometrial adenocarcinomas were well distinguished by claudins 1 and 2 by immunohistochemistry, claudins 3, 4, and 7, however, did not prove useful in distinguishing the two entities. The similar claudin pattern seen in hyperplasia and endometrioid carcinoma and the differences regarding seropapillary adenocarcinoma support the dualistic model of endometrial carcinogenesis. The claudin pattern of the two tumor types might reflect a different cellular or pathogenetic pathway as well as a different cell adhesion behavior explaining the invasive properties.