APC, β-catenin, and E-cadherin and the development of recurrent endometrial carcinoma

Abstract

Endometrial carcinoma, generally, has a good prognosis. However, in some patients, the tumor appears to behave very aggressively, a course that cannot be explained with histopathological characteristics. More insight into the molecular background can be valuable to clarify these differences in tumor behavior. The three components associated with the Wnt pathway – i.e., adenomatous polyposis coli (APC), β-catenin, and E-cadherin – were evaluated in a case-control study of 28 patients with stage-I endometrial carcinomas to determine their involvement in the development of recurrent disease. Mutation analysis of the mutation cluster region of theAPCgene, determination of gene promoter methylation status of theAPC-1AandE-cadheringenes, and immunohistochemical analysis of APC, E-cadherin, and β-catenin were performed using paraffin-embedded tumor tissue. Twenty-oneAPCgene mutations were detected in 12 of 28 (43%) patients. Only three mutations would result in a stopcodon in theAPCgene.APCgene promoter methylation was assessed in 12 of 28 (43%) patients. APC immunostaining was absent in two of 24 (8.3%) patients. The occurrence ofAPCmutations,APCgene promoter methylation, and APC immunostaining were not predictive for recurrence. No E-cadherin expression was observed in four of 24 patients (17%).E-cadheringene promoter methylation could not be detected in any of the patients. The absence of E-cadherin expression was predictive for distant metastases, but not for local recurrence. Nuclear localization of β-catenin was present in nine of 24 (38%) patients and was not predictive for recurrent disease. Involvement of epigenetic and genetic aberrations inAPCand β-cateningenes seems to be of minor importance for the development of local recurrences and distant metastases. Although the number of patients is limited, E-cadherin expression appears to be predictive for the development of distant metastases in endometrial carcinoma.