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

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.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Genetic: Descriptive and analytical

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 Type: Observational
• Enrollment (Estimated): 64

Contacts and Locations

• Study Contact: Name: David F Cantu-de-León, PhD; Phone Number: 21016 +52-55-5628-0400; Email: dfcantu@gmail.com
• Study Contact Backup: Name: Diddier Prada, PhD; Phone Number: +52-55-41-42-18-02; Email: pradadiddier@gmail.com

Study Locations

• Mexico
  • Cdmx
    • Mexico City, Cdmx, Mexico, 14080
      • Recruiting
      • Instituto Nacional de Cancerologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The investigators will evaluate samples from 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) for the detection of POLE mutations.

Description

Criteria: 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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with EC endometroid; Patients with EC endometroid subtype and peripheral blood, treated during 2015-2019 at the INCan.	Genetic: Descriptive and analytical; Patients with EC endometroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sequence the exome	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).	2024-2025
Determine POLE mutations	Determine POLE mutations by massive next-generation sequencing of a discovery cohort in patients with endometroid-type EC.	2024-2025
Determine microsatellite instability	To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC.	2025-2026
Validation	To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC.	2025-2026

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Institute of Cancerología
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: David F Cantu-de-León, PhD, The Principal Investigator

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Endometrial cancer; Prognostic factors
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms
• Other Study ID Numbers: (023/028/ICI/(CEI/017/23)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Any time by direct request to the principal investigator
• IPD Sharing Access Criteria: Only for research purposes.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No