Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers

PLoS One. 2013 Nov 7;8(11):e79737. doi: 10.1371/journal.pone.0079737. eCollection 2013.

Abstract

Background: 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. We aimed to study the prevalence of LS among EC patients in our population.

Methods: Universal 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.

Results: One 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.

Conclusion: The 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology*
  • DNA Methylation
  • DNA Mismatch Repair
  • Endometrial Neoplasms / complications*
  • Endometrial Neoplasms / diagnosis
  • Female
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • Microsatellite Instability
  • Middle Aged
  • MutL Protein Homolog 1
  • Neoplasm Grading
  • Neoplasm Staging
  • Nuclear Proteins / genetics
  • Prevalence

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • MutL Protein Homolog 1

Grants and funding

This study was supported by Conselleria Sanidad Comunidad Valenciana, Spain (AP/177/10) (http://www.san.gva.es/); Biomedical Research Foundations of the Alicante University Hospital (PI14/2006 and NI02/2011) (http://www.dep19.san.gva.es/); and the Elche University Hospital, Spain (FIBElx-CO11/03) (http://www.dep20.san.gva.es/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.