The Role of CTNNB1 in Endometrial Cancer

Abstract

Endometrial cancer (EC) is the most common gynaecologic malignancy in the developed countries. Recent evidence suggests that histopathological subtyping together with molecular subgrouping can lead to more accurate assessment of the risk profile for the patient. Clinical studies suggest the currently used molecular classification improves the risk assessment of women with endometrial cancer but does not explain the differences in recurrence profiles clearly. This could be improved by novel markers. One of such are mutations in the β-catenin (CTNNB1) gene, a frequently mutated gene in endometrial cancer. This shows mutations mostly at phosphorylation sites of the β-catenin and almost exclusively in the endometrial subgroup of no specific molecular profile. CTNNB1 mutations lead to alterations in the Wnt/β-catenin signalling pathway, involved in the carcinogenesis and progression of EC by inducing transcription of target genes, whose function is to regulate the cell cycle. Although tumours with mutations in CTNNB1 tend to have low-risk characteristics, they are related to worse outcomes with significantly increased rate of disease recurrence and lower overall survival.