Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on Prognosis

Recruiting

• Conditions: Endometrial Cancer
• Interventions: Genetic: Descriptive and analytical

• Registration Number: NCT06206083
• Lead Sponsor: National Institute of Cancerología

Brief Summary

Endometrial cancer (EC) is one of the most common gynecological neoplasms, being the second in incidence and third in mortality in Mexico. Recent studies show that EC molecular classification (Cancer Genome Atlas Research Network, 2013) serves to establish a more accurate prognosis in these patients and regulate therapeutic behavior in a personalized manner. However, there are no studies on EC molecular classification in Mexican women or its impact on prognosis and the possible modification of targeted treatment. The investigators will determine the molecular classification in EC by next-generation sequencing (NGS) to detect TP53 and POLE somatic mutations, and immunohistochemical detection of microsatellite instability (MSH2, MLH1, PMS1, PMS2, MSH6, and MSH3) in a cohort of patients with endometrioid-type EC, endometrioid subtype, attended at the Instituto Nacional de Cancerología - Mexico (INCan) and determine its impact on clinical prognosis.

Detailed Description

The investigators will carry out a pilot study on patients with endometrioid type EC treated between 2015-2019. Samples of patients over 18 years of age admitted to the cohort with a diagnosis of endometrioid-type EC are already collected and will be evaluated for exome sequencing (N=32) and the detection of POLE mutations. DNA will be extracted using the "DNA/RNA AllPrep" kit (QIAGEN). Verification of adequate DNA extraction will be performed by quantifying using TapeStation (Agilent). Exome sequencing (N = 32 tumor samples and 32 somatic samples \[leukocytes\] from the same patient) will be carried out using Illumina's Nextera Rapid Capture Exome at Azenta Life Science (NJ, USA) following preset protocols and with a depth of 100X. The alignment and detection of variants will be done with the GATX-Mutect Suite (Broad Institute, USA) and the annotation of variant filtering with ANNOVAR. The identification of hotspots will be made according to Chen study. The immunohistochemistry (IHC) for microsatellite instability and overexpressed mutant TP53 (N = 94) will be done using established IHC protocols and will include MSH2, MLH1, PMS1, PMS2, MSH6, MSH3, and TP53.

Study Timeline

• Study First Submitted: 2023-12-05
• Study First Submitted QC: 2024-01-12
• Study First Posted: 2024-01-16
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-27
• Last Update Posted: 2024-02-28
• Study Start: 2024-03-01
• Primary Completion: 2026-11-01
• Study Completion: 2027-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 64

Inclusion Criteria

• Clinical diagnosis of endometrioid-type endometrial cancer with samples available
• That the patients have undergone surgery at INCan.

Exclusion Criteria

• Samples with CEE of non-endometroid type.
• Samples from patients with double primary neoplasm, including carcinoma ductal in situ, squamous cell skin cancers, and cervical carcinoma in situ
• History of malignancy < 5 years prior with no evidence of disease (i.e., remission).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with EC endometroid	Descriptive and analytical	Patients with EC endometroid subtype and peripheral blood, treated during 2015-2019 at the INCan.

Primary Outcome Measures

Name	Time	Method
Validation	2025-2026	To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC.
sequence the exome	2024-2025	Molecular classification of endometroid-type endometrial cancer in Mexican participants based on POLE and TP53 mutations as well as makers of microsatellite instability (MSH2, MLH1, PMS1, PMS2, MSH6, and MSH3).
Determine POLE mutations	2024-2025	Determine POLE mutations by massive next-generation sequencing of a discovery cohort in patients with endometroid-type EC.
Determine microsatellite instability	2025-2026	To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC.

Secondary Outcome Measures

Name	Time	Method
Disease-free surviva	2025-2026	To describe the disease-free survival of the molecular types of endometroid-type EC in INCan patients.
Overall survival	2025-2026	To describe the overall survival of molecular types of endometroid-type EC in INCan patients.

Trial Locations

Locations (1)

Instituto Nacional de Cancerología; 🇲🇽 Mexico City, Cdmx, Mexico