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Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.

Methods

A total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.

Results

A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (n = 64) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of MSH2 on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.

Conclusions

Strict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients.

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Authors and Affiliations

  1. Department of Digestive Surgery, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris, France

    Guillaume Canard MD, Jeremie H. Lefevre MD, Conor Shields MD, Emmanuel Tiret MD & Yann Parc MD, PhD

  2. Department of Oncogenetics, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France

    Chrystelle Colas MD, Florence Coulet PharmD, PhD & Florent Soubrier MD, PhD

  3. Department of Pathology, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris, France

    Magali Svrcek MD, PhD & Jean-Francois Fléjou MD, PhD

  4. Department of Biology and Molecular Genetics, Hôpital Saint-Antoine, Université Pierre et Marie Curie, Paris, France

    Olivier Lascols MD

  5. INSERM UMRS 938, Equipe Instabilité des microsatellites et Cancer, Université Pierre et Marie Curie, Paris, France

    Richard Hamelin PhD & Alex Duval MD, PhD

Authors
  1. Guillaume Canard MD
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  2. Jeremie H. Lefevre MD
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  3. Chrystelle Colas MD
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  4. Florence Coulet PharmD, PhD
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  5. Magali Svrcek MD, PhD
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  9. Alex Duval MD, PhD
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  11. Florent Soubrier MD, PhD
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  13. Yann Parc MD, PhD
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Correspondence to Jeremie H. Lefevre MD.

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Canard, G., Lefevre, J.H., Colas, C. et al. Screening for Lynch Syndrome in Colorectal Cancer: Are We Doing Enough?. Ann Surg Oncol 19, 809–816 (2012). https://doi.org/10.1245/s10434-011-2014-7

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  • DOI: https://doi.org/10.1245/s10434-011-2014-7

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