Determining the Prevalence of Muir-Torre Syndrome in Patients With Lynch Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Prevalence of Muir-Torre syndrome (MTS) in the population of patients with Lynch syndrome
研究概览
简要总结
The main aim of this study is to determine the prevalence of Muir-Torre syndrome (MTS) in the population of patients with Lynch syndrome (LS) confirmed by genetic analysis. Other aims include describing the dermatological clinical manifestations of these patients in order to describe any possible new cutaneous manifestations of this syndrome. Another aim is to use molecular biology (microsatellite instability) and immunohistochemistry to analyze non-sebaceous skin lesions and deep-seated tumors that do not belong to the narrow spectrum of Lynch syndrome, and determine whether their occurrence in these patients is related to the genetic syndrome. The follow-up of these tumors (screening for new tumors) in patients with SL, as recommended by the learned societies, will also be evaluated. Finally, a biobank of cutaneous and deep tumour lesions in paraffin (retrospective) and smears of cutaneous lesions and healthy tissue (prospective) will be set up.
详细描述
Muir-Torre Syndrome (MTS) is an autosomal dominant disease described independently by Muir et al. in 1967 and Torre in 1968, defined by the association of a visceral tumor of the Lynch spectrum (colorectal, endometrial, urinary excretory tract, biliary tract, small intestine, stomach or glioblastoma carcinomas) and sebaceous skin tumors and/or multiple keratoacanthomas.
Histo-molecular examination of tumors for TMS/SL is based on 2 techniques, each focusing on a different aspect of TMS pathophysiology.
Immunohistochemistry (IHC) studies the presence of proteins from the MisMatch Repair (MMR) system in lesional tissues, and an absence of expression of one of these proteins is the physical translation of an abnormality in the MMR pathway, for which the presence of a constitutional mutation in one of the MMR system genes (MLH1, PMS2, MSH2, MSH6) is responsible. An IHC-deficient MMR phenotype (dMMR) results in a complete loss of expression of one or more MMR proteins in tumor cells, with expression maintained in "normal" cells (connective cells, immune cells, non-tumor epithelial cells).
Molecular biology or microsatellite instability (MSI) testing focuses on the molecular repercussions of MMR pathway failure. The aim of this technique is to determine the presence of microsatellite marker instability in tumor tissue. While for colorectal tumors, a comparative analysis of the patient's healthy tissue can be dispensed with, for other organs on the Lynch spectrum, including sebaceous tumors, a comparison with DNA from normal tissue can help interpret the results.
The incidence of TMS among patients with genetically proven SL is poorly known. Two studies have shown a prevalence of 9.2%, both involving American patients (1,2). These were 2 retrospective chart-based studies, the skin tumors not having been re-read for diagnostic confirmation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with a germline alteration of one of the MMR (MisMatch Repair) pathway genes (MLH1, PMS2, MSH2, MSH6) proven by constitutional genetic analysis (genetically authenticated Lynch syndrome).
- •Patient followed at Nîmes University Hospital.
- •Patient having given free and informed consent.
- •Person affiliated to or benefiting from a social security scheme.
排除标准
- •Person under court protection, guardianship or curatorship.
- •A person who is unable to give consent.
- •Person for whom it is impossible to give informed information.
研究组 & 干预措施
Patients with Lynch syndrome undergoing screening for Muir-Torre syndrome
干预措施: Sampling of suspected skin lesions (in accordance with good care practices). (Diagnostic Test)
Patients with Lynch syndrome undergoing screening for Muir-Torre syndrome
干预措施: Constitution of a biobank (Genetic)
结局指标
主要结局
Prevalence of Muir-Torre syndrome (MTS) in the population of patients with Lynch syndrome
时间窗: Up to 6 months after inclusion
Proportion of patients with Muir-Torre Syndrome confirmed by the occurrence of a sebaceous tumor (sebaceous adenoma, sebaceoma, sebaceous carcinoma) or several keratoacanthomas among patients with Lynch Syndrome. These tumors may or may not have had the mismatch repair system analyzed by immunohistochemistry (analysis of the 4 antibodies MLH1, PMS2, MSH2, MSH6) or by molecular biology (search for microsatellite instability). If the mismatch repair system has been studied, it must be deficient and the proteins absent on immunohistochemistry must be consistent with the mutated gene in Lynch Syndrome. If a block or slides are still available, sebaceous skin tumors or keratoacanthomas will be re-evaluated at Nîmes University Hospital for confirmation of the diagnosis.
次要结局
- Dermatological clinical manifestations in patients with confirmed Lynch Syndrome(Up to 6 months after inclusion)
- Non-sebaceous skin lesions and Deep-seated tumors not belonging to the narrow spectrum of Lynch syndrome. Presence of antibody MLH1(Up to 6 months after inclusion)
- Non-sebaceous skin lesions and Deep-seated tumors not belonging to the narrow spectrum of Lynch syndrome. Presence of antibody PMS2(Up to 6 months after inclusion)
- Non-sebaceous skin lesions and Deep-seated tumors not belonging to the narrow spectrum of Lynch syndrome. Presence of antibody MSH2(Up to 6 months after inclusion)
- Non-sebaceous skin lesions and Deep-seated tumors not belonging to the narrow spectrum of Lynch syndrome. Presence of antibody MSH6(Up to 6 months after inclusion)