Familial Cancer

, Volume 9, Issue 2, pp 131–139 | Cite as

Clinical and histomolecular endometrial tumor characterization of patients at-risk for Lynch syndrome in South of Brazil

  • Silvia Liliana Cossio
  • Patricia Koehler-Santos
  • Suzana Arenhart Pessini
  • Heleuza Mónego
  • Maria Isabel Edelweiss
  • Luise Meurer
  • Abdellatif Errami
  • Jordy Coffa
  • Hugo Bock
  • Maria Luiza Saraiva-Pereira
  • Patricia Ashton-Prolla
  • João Carlos Prolla


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.


Endometrial cancer Immunohistochemistry Lynch syndrome Methylation analysis Microsatellite instability Mismatch repair 



Colorectal cancer




deoxyribonucleotide acid


Endometrial cancer


Familial history


Fundação de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre




MutL homolog 1


Mismatch repair


MutS homolog 2


MutS homolog 6


Microsatellite stability


Microsatellite instability


Methylation specific multiplex ligation-dependent probe amplification


Polymerase chain reaction


Postmeiotic segregation increased 2


Single strand conformational polymorphism


Tris base, ethylenediaminetetracetic acid, disodium salt


Universidade Federal do Rio Grande do Sul



We are indebted to the patients and their family members who agreed to participate in this study and to Fundação de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPe-HCPA) and Programa de Pós-Graduação em Ciências Gastroenterológicas (UFRGS) who provided funding for this study. We also thank Drs. Miguel Varela and Gabriel Prolla for patient referrals. We are also indebted to Jan Schouten (MRC-Holland, Amsterdam, The Netherlands) for the technical support with MS–MLPA. We thank Dr Vinicius Duval da Silva and Thiago Giugliani (Laboratório de Patología, Hospital São Lucas, Porto Alegre, Brazil) for their stimulating discussions and technical support in IHC protocols, and Aishameraine Venes Schmidt (UFRGS) for help with the data analyses.


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Silvia Liliana Cossio
    • 1
    • 2
    • 3
  • Patricia Koehler-Santos
    • 2
    • 4
  • Suzana Arenhart Pessini
    • 5
    • 6
  • Heleuza Mónego
    • 7
  • Maria Isabel Edelweiss
    • 8
    • 9
  • Luise Meurer
    • 8
    • 9
  • Abdellatif Errami
    • 10
  • Jordy Coffa
    • 10
  • Hugo Bock
    • 11
    • 12
  • Maria Luiza Saraiva-Pereira
    • 13
    • 14
  • Patricia Ashton-Prolla
    • 15
    • 16
    • 3
  • João Carlos Prolla
    • 1
    • 8
  1. 1.Programa de Pós-Graduação em Medicina: Ciências GastroenterológicasUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  2. 2.Laboratório de Medicina Genômica, Centro de Pesquisa ExperimentalHospital de Clínicas de Porto Alegre (HCPA)Porto AlegreBrazil
  3. 3.Instituto Nacional de Genética Médica Populacional (INAGEMP)Porto AlegreBrazil
  4. 4.Programa de Pós-Graduação em Medicina: Ciências MédicasUFRGSPorto AlegreBrazil
  5. 5.Complexo Hospitalar Santa Casa de Porto AlegrePorto AlegreBrazil
  6. 6.Universidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil
  7. 7.Serviço de Ginecologia e ObstetríciaHCPAPorto AlegreBrazil
  8. 8.Serviço de PatologiaHCPAPorto AlegreBrazil
  9. 9.Departamento de PatologiaUFRGSPorto AlegreBrazil
  10. 10.MRC-HollandAmsterdamThe Netherlands
  11. 11.Laboratório de Identificação Genética, Centro de Pesquisa ExperimentalHCPAPorto AlegreBrazil
  12. 12.Programa de Pós-Graduação em Biologia Celular e MolecularUFRGSPorto AlegreBrazil
  13. 13.Departamento de BioquímicaUFRGSPorto AlegreBrazil
  14. 14.Serviço de Genética Médica and Laboratório de Identificação Genética, Centro de Pesquisa ExperimentalHCPAPorto AlegreBrazil
  15. 15.Departamento de GenéticaUFRGSPorto AlegreBrazil
  16. 16.Serviço de Genética Médica, Laboratório de Medicina Genômica, Centro de Pesquisa ExperimentalHCPAPorto AlegreBrazil

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