Simultaneous immunohistochemical localization of β-catenin and cyclin D 1 in differentiated but not in undifferentiated human endometrial carcinoma

Purpose: Beta-catenin plays dual important roles in epithelial cell-cell adhesion in cytoplasm as well as in the nuclear T-cell factor (TCF)/lymphoid enhancing factor-1 (LEF-1) signaling pathway. Abnormal nuclear accumulation of beta-catenin promotes colorectal carcinogenesis by triggering the expression of cyclin D1 gene through the TCF/LEF-1 pathway. The purpose of this study was to investigate the possible involvement of the TCF/LEF-1 pathway in endometrial carcinogenesis.

Methods: Immunohistochemical localization of beta-catenin and cyclin D1 in normal endometrium, hyperplastic endometrium and endometrial carcinoma were assessed on serial tissue sections.

Results: Nuclear accumulation of beta-catenin was observed in endometrial carcinomas compared with normal endometria. Cyclin D1-positive endometrial cancer cases were beta-catenin-positive in the nuclei, especially in 70% (7/10) of G1 and 55.6% (5/9) of G2 differentiated endometrial carcinomas, but never in G3 undifferentiated ones.

Conclusions: These results imply that the simultaneous nuclear accumulation of beta-catenin and cyclin D1--suggesting the activation of the TCF/LEF-1 pathway--may be a potential marker for the progression of Type 1 endometrial carcinogenesis.

β-catenin; Cyclin D1; TCF/LEF pathway; Uterine endometrial carcinoma

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