Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

The Roles of Tricellular Tight Junction Protein Angulin-1/Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Endometriosis and Endometrioid-Endometrial Carcinoma

Tight junction proteins play roles beyond permeability barriers functions and control cell proliferation and differentiation. The relation between tight junctions and the signal transduction pathways affects cell growth, invasion and migration. Abnormality of tight junction proteins closely contributes to epithelial mesenchymal transition (EMT) and malignancy of various cancers. Angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) forms tricellular contacts that has a barrier function. Downregulation of angulin-1/LSR correlates with the malignancy in various cancers, including endometrioid-endometrial carcinoma (EEC). These alterations have been shown to link to not only multiple signaling pathways such as Hippo/YAP, HDAC, AMPK, but also cell metabolism in ECC cell line Sawano. Moreover, loss of angulin-1/LSR upregulates claudin-1, and loss of apoptosis stimulating p53 protein 2 (ASPP2) downregulates angulin-1/LSR. Angulin-1/LSR and ASPP2 concentrate at both midbody and centrosome in cytokinesis. In EEC tissues, angulin-1/LSR and ASPP2 are reduced and claudin-2 is overexpressed during malignancy, while in the tissues of endometriosis changes in localization of angulin-1/LSR and claudin-2 are seen. This review highlights how downregulation of angulin-1/LSR promotes development of endometriosis and EEC and discusses about the roles of angulin-1/LSR and its related proteins, including claudins and ASPP2.

PTEN protein expression has role in predicting disease-free-interval in endometrioid endometrial carcinoma

Objectives To determine the significance of tumour PTEN protein expression in endometrioid endometrial carcinoma (EEC) and it is correlation with tumour characteristics. Methods A total of 30 eligible archived paraffin-embedded tissue blocks from 61 EEC cases (January 2015–December 2017) were retrieved from the Histopathology Laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) following institutional ethic approval. For PTEN protein detection, immunohistochemistry (IHC) staining was performed and the data was correlated with clinicopathologic parameters. Results Fourteen samples (46.7%) showed positive PTEN protein expression, while 16 (53.3%) were negative. The mean age was 62.00 ± 9.51 years old, while the mean Body Mass Index (BMI) was 27.28 ± 7.16 kg/m2. There was no significant difference between age (p=0.27, 95% CI: −10.98 to 3.21) and BMI (p=0.67, 95% CI: −4.30 to 6.58) with PTEN protein expression. There were significant correlation between PTEN protein expression with myometrial invasion (p=0.010), but not with lymphovascular space invasion (p=0.743), grade (p=0.532), stage (p=0.733) and CA-125 level (p=0.47). The higher stage correlates with the presence of LVSI (p=0.002). PTEN positive associated with longer disease-free-interval (p=0.025), but not improving the overall survival (p=0.38) Conclusions Positive PTEN protein expression correlates with less myometrial invasion.