beta- and gamma-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability

The activation of the adenomatous polyposis coli (APC)/beta -catenin/T-cell factor (Tcf) pathway due to beta -catenin gene mutation has been recently implicated in the development of some endometrial carcinomas. beta- And gam ma -catenin are structurally and functionally related molecules that partic ipate in cell adhesion and signal transduction. Nuclear accumulation of bet a- and gamma -catenin have been related to the activation of the APC/beta - catenin/Tcf pathway. In this study, we investigate the immunohistochemical expression pattern (nuclear vs membranous) of beta- and gamma -catenin in 4 0 endometrial carcinomas and their correlation with clinicopathological fea tures and microsatellite instability (MI) status. MI was detected at three or more loci in 12 tumors: 11 were endometrioid and one was non-endometrioi d. Nuclear catenin expression was found in 13 carcinomas: ten carcinomas ha d nuclear beta -catenin expression and three carcinomas had nuclear gamma - catenin expression. The nuclear catenin expression pattern significantly co rrelated with the histological type, International Federation of Gynecology and Obstetrics (FIGO) grade, and the presence of a second neoplasm. Nuclea r catenin expression was always observed in low-grade endometrioid carcinom as; it was also more frequently associated with a second carcinoma. No corr elation was observed between the catenin expression pattern and the level o f myometrial infiltration, stage, associated endometrial hyperplasia, the e xistence of a source of estrogenic stimulation, and MI. However, four of 13 endometrioid carcinomas in this series had both catenin nuclear expression and MI. These data suggest that at least two different neoplastic pathways can lead to endometrial carcinomas with an endometrioid phenotype. In one, MI would be a key event, while in the other, the APC/beta -catenin/Tcf sig naling pathways could be activated. Probably, in some cases, both pathways could simultaneously occur.