Lynch syndrome identification in a Brazilian cohort of endometrial cancer screened by a universal approach - PubMed

Lynch syndrome identification in a Brazilian cohort of endometrial cancer screened by a universal approach - PubMed

Lynch syndrome identification in a Brazilian cohort of endometrial cancer screened by a universal approach

Reginaldo Cruz Alves Rosa 1, Jessica Oliveira Santis 2, Lorena Alves Teixeira 3, Greice Andreotti Molfetta 4, Jennifer Thalita Targino Dos Santos 5, Vanessa Dos Santos Ribeiro 6, Fernando Chahud 7, Alfredo Ribeiro-Silva 8, Mariângela Ottoboni Brunaldi 9, Wilson Araújo Silva Jr 10, Victor Evangelista de Faria Ferraz 11

Affiliations 

• PMID: 32694065
 
• DOI: 10.1016/j.ygyno.2020.07.013

Abstract

Objective: To report the frequency of Lynch syndrome (LS) in a cohort of patients from Southeast Brazil bearing endometrial cancer (EC), using a tumor screening universal approach.

Methods: A total of 242 endometrial carcinomas were screened by immunohistochemistry (IHC) and microsatellite instability (MSI) for detection of DNA mismatch repair deficiency (dMMR). MLH1 methylation was assessed to identify sporadic cases. Patients with dMMR tumors were recruited for germline variant analysis by next-generation sequencing of the MLH1, MSH2, MSH6, PMS2, and EPCAM genes.

Results: Ninety-three out of 242 tumors (38.5%) were classified as dMMR based on MSI and IHC results. Of these, 54 cases were selected for germline analysis, and 37/54 (68.5%) were available for sequencing. Ten patients (10/37, 27%) harbored germline pathogenic or likely pathogenic variants, most of them in the MSH6 gene (4/10, 40%). Seven variants of uncertain significance were found. Eight novel germline variants were identified. The LS prevalence in our cohort was of at least 4.1%. LS patients presented lower mean age at cancer diagnosis compared with patients diagnosed with sporadic EC. Individuals with dMMR tumors, without germline pathogenic variants detected in LS-genes ("Lynch-like" syndrome), had an intermediate mean age at cancer diagnosis between LS and sporadic cases.

Conclusion: This is the first report of the LS prevalence in EC screened by a universal approach in Brazil. Our findings contribute to a better understanding of the mutational landscape of this syndrome in Brazil, which is relevant for improved identification, genetic counseling, prevention and control of cancer in LS.

Keywords: Brazil; Endometrial cancer; Lynch syndrome; Lynch-like syndrome; Next-generation sequencing; Universal screening.

Copyright © 2020 Elsevier Inc. All rights reserved.

Conflict of interest statement

Declaration of competing interest The authors declared no potential conflicts of interest regarding the research, authorship, and/or publication of this article.