Status
Conditions
Treatments
About
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.
Full description
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.
These patients may also develop skin tumors not belonging to the SMT-SL spectrum, such as basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs) or melanocytic tumors (melanomas and nevi). These skin and deep tumors (visceral tumors) not belonging to the Lynch spectrum of patients with proven SL have rarely been systematically studied for a dMMR phenotype.
French societies (INCa, Société Française de Gastroentérologie) have proposed the management of any patient with a mutation in one of the MMR system genes. Compliance with follow-up is a major public health issue. Digestive follow-up (regular colonoscopies) is only 68%, whereas gynecological follow-up is only 73% to 80%. Other types of follow-up, notably dermatological, have rarely been analyzed, and above all we have no data on compliance in France.
Enrollment
Sex
Volunteers
Inclusion criteria
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
150 participants in 1 patient group
Loading...
Central trial contact
Eric FROUIN, Dr.; Anissa MEZGARI
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal