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Early-Onset Colorectal Cancer is an Easy and Effective Tool to Identify Retrospectively Lynch Syndrome

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

Abstract

Background and Objectives

Early age of onset is a marker of a possible hereditary component in colorectal cancer (CRC). We evaluated whether early age of onset is a good marker to identify Lynch syndrome, especially retrospectively, and if there is any other feature that could improve this identification.

Methods

We selected patients with CRC aged 45 years or younger from the pathological reports of three different institutions and different periods of time. Clinical information, family history, and tumor samples were obtained. Cases were classified according to mismatch repair (MMR) proficiency.

Results

Of 133 tumors, 22 showed microsatellite instability (MSI). In 15 MSI cases, a germline mutation in 1 of the MMR genes was identified, 7 of which were not identified before. The positive predictive value (PPV) of right colon CRC for a positive genetic MMR test is 30.6%, whereas “signet ring” cells and fulfillment Amsterdam II criteria have PPVs of 42.9% and 47.8%, respectively. Combining right-sided CRC with mucin production, with fulfilling Amsterdam II criteria, or with “signet ring” cells, PPVs are 54.5, 64.3, and 100%. The probability of the absence of a mutation when CRC is located in the left colon is 94.7%, whereas absence of aggregation for Lynch-related neoplasm has a 100% probability.

Conclusions

Early age of onset is an effective method to identify retrospectively Lynch syndrome. Taking into account the location and histology features of the tumor, and the familial history of the cases, we notably increase the a priori probability of detecting a germline MMR mutation.

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Acknowledgment

This work was funded by the Mutua Madrileña Foundation (Project P133-08). The authors thank the Pathology Departments of Gregorio Marañón University Hospital, Segovia Hospital, and 12 de Octubre University Hospital for providing us with the paraffin-embedded tissues, and Ron Hartong for his help with the English redaction of the article.

Disclosure

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Surgery Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    José Perea MD, PhD, Edurne Álvaro MD, Cristina Alegre MD, Irene Osorio MD, Manuel Lomas MD, PhD & Manuel Hidalgo MD, PhD

  2. Pathology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Yolanda Rodríguez MD & Francisco Colina MD, PhD

  3. Molecular Biology Laboratory, Hospital Universitario 12 de Octubre, Madrid, Spain

    Daniel Rueda PhD

  4. Gastroenterology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    José C. Marín MD & José Díaz-Tasende MD

  5. Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    Javier Benítez PhD & Miguel Urioste MD, PhD

  6. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain

    Javier Benítez PhD & Miguel Urioste MD, PhD

Authors
  1. José Perea MD, PhD
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  2. Yolanda Rodríguez MD
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  3. Daniel Rueda PhD
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  4. José C. Marín MD
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  5. José Díaz-Tasende MD
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  6. Edurne Álvaro MD
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  7. Cristina Alegre MD
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  8. Irene Osorio MD
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  9. Francisco Colina MD, PhD
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  10. Manuel Lomas MD, PhD
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  11. Manuel Hidalgo MD, PhD
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  12. Javier Benítez PhD
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  13. Miguel Urioste MD, PhD
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Corresponding author

Correspondence to José Perea MD, PhD.

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Perea, J., Rodríguez, Y., Rueda, D. et al. Early-Onset Colorectal Cancer is an Easy and Effective Tool to Identify Retrospectively Lynch Syndrome. Ann Surg Oncol 18, 3285–3291 (2011). https://doi.org/10.1245/s10434-011-1782-4

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  • DOI: https://doi.org/10.1245/s10434-011-1782-4

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