Molecular Classification in Mexican Patients With Endometrial Cancer and Its Impact on Prognosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Validation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of endometrioid-type endometrial cancer with samples available
- •That the patients have undergone surgery at INCan.
排除标准
- •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).
结局指标
主要结局
Validation
时间窗: 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
时间窗: 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
时间窗: 2024-2025
Determine POLE mutations by massive next-generation sequencing of a discovery cohort in patients with endometroid-type EC.
Determine microsatellite instability
时间窗: 2025-2026
To perform validation of POLE mutation by real-time PCR in a validation cohort of patients with endometroid-type EC.
次要结局
- Disease-free surviva(2025-2026)
- Overall survival(2025-2026)
研究者
David Cantu
Doctor in Medical Sciences; Researcher in Medical Sciences
National Institute of Cancerología