BACKGROUND: Uterine endometrial cancer is the fourth major female neoplasm. Its risk factors such as obesity, hypertension, diabetes mellitus, infertility, and so on, are deeply related to life custom and not easily avoided. Preventive method of this cancer would be blockade of the pathway of tumor development, which has not been clearly understood. METHODS: The paraffin-embedded surgical sections of 53 cases of uterine endometrial cancer were immunohistochemically analyzed for WNT1 and β-catenin. RESULTS: Cytoplasmic expression of WNT1 was found limitedly in specimens of early stages. Membranous and cytoplasmic expressions of β-catenin were found in most cases except for highly advanced ones, however nuclear localization of β-catenin was found at tumor development, such as carcinogenesis and squamous differentiation in early-stage cases. WNT1 and β-catenin were simultaneously expressed at the area of adenocarcinoma in situ arising within adenoma. Strong expressions of WNT-1 and nuclear localization of β-catenin were also seen at the branching elements of adenocarcinoma glands, where thereafter formed morules. WNT1 was expressed at the lymphatic invasion, where neither membranous nor nuclear expression of β-catenin was found. At lymph node metastasis, only WNT1 was intensely expressed. CONCLUSIONS: Wnt signaling pathway is considered to be involved at the initial period of tumor development in uterine endometrial cancer. WNT1 is also supposed to initiate distant metastasis. It could provide the concept of cancer prevention that Wnt inhibitory agents might prevent the carcinogenesis from precancerous status and the distant metastasis.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA