The activation of the APC/b-catenin signalling pathway due to b-catenin mutations has been implicated in the development of a subset of endometrial carcinomas (ECs). However, up to 25% of ECs have b-catenin nuclear accumulation without evidence of b-catenin mutations, suggesting alterations of other molecules that can modulate the Wnt pathway, such as APC, g-catenin, AXIN1 and AXIN2. We investigated the expression pattern of b-and g-catenin in a group of 128 endometrial carcinomas, including 95 endometrioid endometrial carcinomas (EECs) and 33 non-endometrioid endometrial carcinomas (NEECs). In addition, we evaluated the presence of loss of heterozygosity and promoter hypermethylation of the APC gene and mutations in the APC, b-and g-catenin, AXIN1, AXIN2, and RAS genes, and phospho-Akt expression. No APC mutations were detected but LOH at the APC locus was found in 24.3% of informative cases. APC promoter 1A hypermethylation was observed in 46.6% of ECs, and was associated with the endometrioid phenotype (P=0.034) and microsatellite instability (P=0.008). Neither LOH nor promoter hypermethylation of APC was associated with nuclear catenin expression. Nuclear b-catenin expression was found in 31.2% of EECs and 3% of NEECs (P=0.002), and was significantly associated with b-catenin gene exon 3 mutations (P50.0001). b-catenin gene exon 3 mutations were associated with the endometrioid phenotype, and were detected in 14 (14.9%) EECs, but in none of the NEECs (P=0.02). g-catenin nuclear expression was found in 10 ECs; it was not associated with the histological type but was associated with more advanced stages (P=0.042). No mutations in g-catenin, AXIN1 and 2 genes were detected in this series. Neither RAS mutations nor phospho-Akt expression, which were found in 16 and 27.6% of the cases, respectively, were associated with bcatenin nuclear expression. Our results demonstrated a high prevalence of alterations in molecules of the APC/ b-catenin pathway, but only mutations in b-catenin gene are associated with aberrant nuclear localization of bcatenin.

Abnormal expression of cadherins and catenins plays a critical role in the initiation and progression of multiple human tumours. This study aimed to evaluate the immunoreactivity of E- and P-cadherin, beta- and gamma-catenin, and p120ctn in premalignant and malignant endometrial lesions and to correlate their membranous expression with clinicopathological features. In addition, we examined whether or not LOH and promoter hypermethylation of the CDH1 gene were associated with E-cadherin expression and clinicopathological variables. Finally, we studied the frequency of beta-catenin mutations in premalignant endometrial lesions. Immunohistochemical staining was performed in 21 atypical endometrial hyperplasias (AEHs), 95 endometrioid carcinomas (EECs), and 33 non-endometrioid carcinomas (NEECs). Reduced E-cadherin expression was observed in 57.8% of the cases, being more frequent in NEECs (87.1%, p = 0.001) and carcinomas of more advanced stage (85.7% of stage III-IV carcinomas, p = 0.01). LOH of CDH1 gene was found in 57.1% of NEECs but only in 22.5% of EECs (p = 0.011) and showed a trend towards association with reduced E-cadherin expression (p = 0.089). CDH1 promoter hypermethylation was found in 21.2% of endometrial carcinomas but was not associated with clinicopathological or immunohistochemical variables. Reduced expression of beta- and gamma-catenin and p120ctn was found in 76.1%, 94.3%, and 63.6% of the cases, respectively, being more frequent in lesions with reduced E-cadherin expression. In addition, beta-catenin, but not gamma-catenin or p120ctn expression, was associated with the histology of the lesion, since it was reduced in 35% of AEHs, 80.3% of EECs, and 96.9% of NEECs (p = 0.000). Mutations in exon 3 of the beta-catenin gene, associated with beta-catenin nuclear expression, were detected in 3 (14.0%) AEH, a frequency similar to that previously reported in this series of ECs. Finally, upregulation of P-cadherin was observed in 28.6% of cases. This alteration was associated with the histology of the lesion, since it was found in 9.5% of AEHs, 27.7% of EECs, and 46.2% of NEECs (p = 0.021).

No abstract

Objetivo: Analizar las cesáreas realizadas en nuestro centro agrupándolas según la clasificación de Robson para establecer medidas que permitan reducir la tasa de cesáreas. Método: Auditoría prospectiva de los nacimientos asistidos en el Hospital Doctor Peset en el año 2019 mediante la clasificación de Robson. Resultados: Se han analizado 1113 nacimientos con una tasa de cesárea del 25.3%. El grupo que más contribuyó al total de cesáreas realizadas, con un 34.4%, fue el 2A (nulíparas con feto único en presentación cefálica, de 37 semanas o más de embarazo, que iniciaron el parto mediante inducción). En segundo lugar, el grupo 5 (multíparas con al menos una cesárea previa, con un feto único en presentación cefálica, de 37 semanas o más de embarazo), con un 20.1%. Las inducciones en nulíparas multiplican por tres la tasa de cesárea respecto a las nulíparas que inician el trabajo de parto de manera espontánea. Conclusiones: La clasificación de Robson es una herramienta que permite clasificar y analizar de manera sencilla los grupos en los que implantar medidas para reducir el número de cesáreas realizadas. Analizar las indicaciones de inducción y revisar los protocolos de actuación podría suponer una disminución sustancial en la tasa de cesáreas en nuestro centro.

No abstract