Electronic databases were searched for studies evaluating β-catenin immunohistochemistry in normal endometrium (NE), benign and/or premalignant EH, and endometrioid carcinoma (EC).
ECCs less frequently harboured mutations affecting CTNNB1 and PTEN but more frequently harboured PPP2R1A and TP53 mutations than non-POLE endometrioid carcinomas from The Cancer Genome Atlas (TCGA).
The KRAS gene was most often mutated in carcinomas next to hyperplastic endometrium, whereas PIK3CA and CTNNB1 mutations were found in endometrioid carcinomas with adjacent atrophic endometrium.
By contrast, CTNNB1 mutations are significantly different in low-grade ovarian endometrioid carcinomas (53%) compared with low-grade endometrial endometrioid carcinomas (28%) (P<0.0057).
Aberrant nuclear beta-catenin expression in the spindle or corded cells in so-called corded and hyalinized endometrioid carcinomas. Another critical role of the unique morphological feature.
A review of the literature indicated that beta-catenin mutations are characteristic of well-differentiated endometrioid carcinomas, since they were present in nearly 60% of grade I but in less of 3% of grade III tumours.
Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations: high-grade serous and possibly endometrioid carcinomas most probably arise from surface epithelial inclusion glands with TP53 mutations and dysfunction of BRCA1 and/or BRCA2; low-grade serous carcinomas probably arise in a stepwise fashion in an adenoma-borderline tumor-carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma via activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF; mucinous carcinomas arise via an adenoma-borderline tumor-carcinoma sequence with mutations in KRAS; low-grade endometrioid carcinomas arise from endometriosis via mutations in CTNNB1 (the gene encoding beta-catenin) and PTEN.
Nuclear immunoreactivities for beta -catenin and CTNNB1 mutations were restricted to independent uterine and ovarian tumors and were absent in all of the metastatic tumors, providing direct evidence for a divergence of molecular oncogenetic mechanisms in the subset of synchronous endometrioid carcinomas.
The most frequent genetic alteration in endometrioid carcinoma is PTEN inactivation by mutation, followed by microsatellite instability (MIN) and mutations of K-ras and beta-catenin.
It has been suggested that the former tumors have the same molecular alterations (microsatellite instability [MSI], PTEN, and beta-catenin) described in endometrioid carcinomas of the uterus.
In the univariate and multivariate survival analyses, beta-catenin nuclear expression was selected as an indicator of good prognosis, because no patient whose tumor expressed beta-catenin in the nuclei showed relapses or died, in contrast to the 19 relapses and deaths among patients with tumors that only had beta-catenin membranous expression, including three of the four patients with endometrioid carcinomas.