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

Обзор

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.

Подробное описание

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.

Вмешательства

• Генная терапия Descriptive and analytical
  Patients with EC endometroid

Первичные конечные точки

• sequence the exome [Срок оценки: 2024-2025]
• Determine POLE mutations [Срок оценки: 2024-2025]
• Determine microsatellite instability [Срок оценки: 2025-2026]
• Validation [Срок оценки: 2025-2026]

Вторичные конечные точки (2)

• Overall survival [Срок оценки: 2025-2026]
• Disease-free surviva [Срок оценки: 2025-2026]

Критерии участия

Criteria: Inclusion Criteria:

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

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Мексика · 1 центр

• Instituto Nacional de Cancerología — Mexico City

Идентификаторы

NCT: NCT06206083 · (023/028/ICI/(CEI/017/23)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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