Prevalence of Lynch Syndrome among Patients with Newly Diagnosed Endometrial Cancers

Cecilia Egoavil,Maria-Isabel Castillejo,Gloria Peiro,Jose-Antonio Lopez,Juan-Carlos Martínez-Escoriza,Lucia Perez-Carbonell,Víctor-Manuel Barberá,Oscar Piñero,Carla Guarinos,Jose-Luis Soto,Adela Castillejo,Sonia Cigüenza,Artemio Paya,Francisco-Ignacio Aranda,Estefanía Rojas,Ana-Beatriz Sánchez-Heras,Maria-Jose Román,Cristina Alenda,Hiromu Suzuki

doi:10.1371/journal.pone.0079737

Abstract

BackgroundLynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC) patients with LS has the potential to influence life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population.MethodsUniversal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI), immunohistochemistry (IHC) for mismatch-repair (MMR) protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed.ResultsOne hundred and seventy-three EC (average age, 63 years) were screened. Sixty-one patients (35%) had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs). Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques.ConclusionThe prevalence of LS among EC patients was 4.6% (8/173); with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended.

Highlights

Identification of hereditary forms of neoplasias among cancer patients is crucial for better management and prevention of other syndrome-associated malignancies for the patients and their families [1]
Additional histopathology features recorded were the presence of lymphovascular invasion (LVI), tumor-infiltrating lymphocytes (TILs), myometrial invasion, and grade and stage according to the International Federation of Obstetrics and Gynaecology (FIGO)
All patients underwent biopsy or hysterectomy and paraffin waxembedded tissues were available for IHC and molecular testing

Summary

Introduction

Identification of hereditary forms of neoplasias among cancer patients is crucial for better management and prevention of other syndrome-associated malignancies for the patients and their families [1]. The incidence is increasing and approximately 5% of cases are thought to result from a genetic predisposition [3]. Lynch syndrome (LS) is an autosomal dominant condition caused by a mutation in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2 [4]. Lynch syndrome (LS) is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC) patients with LS has the potential to influence life-saving interventions. Tumor testing using microsatellite instability (MSI), immunohistochemistry (IHC) for mismatch-repair (MMR) protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sixty-one patients (35%) had abnormal IHC or MSI results. Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques.

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