title: Clinical and histomolecular endometrial tumor characterization of patients at-risk for Lynch syndrome in South of Brazil.
abstract: Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by germline mutations in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. Clinically, Lynch syndrome is characterized by early onset (45 years) of colorectal cancer (CRC), as well as extra-colonic cancer. Male and female carriers of Lynch syndrome-associated mutations have different lifetime risks for CRC and in women endometrial cancer (EC) may be the most common tumor. Whenever Amsterdam criteria are not fulfilled, the currently recommended laboratory screening strategies involve microsatellite instability testing and immunohistochemistry staining of the tumor for the major MMR proteins. The aim of this study was to estimate the frequency of MMR deficiencies in women diagnosed with EC who are at-risk for Lynch syndrome. Thirty women diagnosed with EC under the age of 50 years and/or women with EC and a first degree relative diagnosed with a Lynch syndrome-associated tumor were included. To assess MMR deficiencies four methods were used: multiplex PCR, Single Strand Conformation Polymorphism, Immunohistochemistry and Methylation Specific-Multiplex Ligation-dependent Probe Amplification. Twelve (40%) patients with EC fulfilling one of the inclusion criteria had results indicative of MMR deficiency. The identification of 5 women with clear evidence of MMR deficiency and absence of either Amsterdam or Bethesda criteria among 10 diagnosed with EC under the age of 50 years reinforces previous suggestions by some authors that these women should be considered at risk and always screened for Lynch syndrome after informed consent.
authors.affiliation: Programa de Pós-Graduação em Medicina: Ciências Gastroenterológicas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. slilianacossio@gmail.com
authors.forename: Silvia Liliana
authors.initials: SL
authors.lastname: Cossio
authors.forename: Patricia
authors.initials: P
authors.lastname: Koehler-Santos
authors.forename: Suzana Arenhart
authors.initials: SA
authors.lastname: Pessini
authors.forename: Heleuza
authors.initials: H
authors.lastname: Mónego
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Edelweiss
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Errami
authors.forename: Jordy
authors.initials: J
authors.lastname: Coffa
authors.forename: Hugo
authors.initials: H
authors.lastname: Bock
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
authors.forename: João Carlos
authors.initials: JC
authors.lastname: Prolla
mesh_terms: D001938:Brazil / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D012306:Risk
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; D051718:MutS Homolog 2 Protein