Clinical trial NCT06206083: Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on Prognosis
Official title: Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on Prognosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Endometrial Cancer
Keywords: Endometrial cancer
Prognostic factors
Lead sponsor: National Institute of Cancerología
Sponsor class: OTHER_GOV
Collaborators: name: GlaxoSmithKline
First posted: 2024-01-16
Enrollment: 64
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: sequence the exome
timeFrame: 2024-2025
measure: Determine POLE mutations
timeFrame: 2024-2025
measure: Determine microsatellite instability
timeFrame: 2025-2026
measure: Validation
timeFrame: 2025-2026
Secondary outcomes:
measure: Overall survival
timeFrame: 2025-2026
measure: Disease-free surviva
timeFrame: 2025-2026
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerología
state: Cdmx
Study officials:
affiliation: The Principal Investigator
name: David F Cantu-de-León, PhD
role: PRINCIPAL_INVESTIGATOR
References: