Chapter 17. Lynch Syndrome (HNPCC)

  1. Prof. Dr. Heike Allgayer PhD2,
  2. Prof. Dr. Helga Rehder3 and
  3. Prof. Dr. Simone Fulda4
  1. Gabriela Möslein

Published Online: 21 AUG 2009

DOI: 10.1002/9783527627523.ch17

Hereditary Tumors: From Genes to Clinical Consequences

Hereditary Tumors: From Genes to Clinical Consequences

How to Cite

Möslein, G. (2008) Lynch Syndrome (HNPCC), in Hereditary Tumors: From Genes to Clinical Consequences (eds H. Allgayer, H. Rehder and S. Fulda), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527627523.ch17

Editor Information

  1. 2

    University of Heidelberg and DKFZ (German Cancer Research Center) Heidelberg, Medical Faculty Mannheim, Chair of Experimental Surgery, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany

  2. 3

    Medical University Vienna, Department of Medical Genetics, Währinger Strasse 10, 1090 Wien, Austria

  3. 4

    Ulm University Children's Hospital, Eythstrasse 24, 89075 Ulm, Germany

Author Information

  1. St. Josefs Hospital Bochum-Linden (Helios), Department of Visceral Surgery Coloproctology, Axtstrasse 35, 44879 Bochum, Germany

Publication History

  1. Published Online: 21 AUG 2009
  2. Published Print: 17 DEC 2008

ISBN Information

Print ISBN: 9783527320288

Online ISBN: 9783527627523

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Keywords:

  • Lynch syndrome;
  • microsatellite instability;
  • immunohistochemistry;
  • mutation analysis;
  • surveillance

Summary

Lynch syndrome (synonymous for HNPCC = hereditary non-polyposis colorectal cancer) is characterized by the development of colorectal, endometrial, gastric, and various other cancers, and is caused by a mutation in one of the mismatch repair (MMR) genes. One of the main challenges in the clinical management of Lynch syndrome remains the broad spectrum and heterogeneity among and between affected families. To date, no clinically relevant genotype-phenotype correlation for the two main affected genes hMSH2 and hMLH1 has been established. Clinical management of familial colorectal cancer (CRC) remains a challenge for clinicians. The overlap of syndromes with different underlying genetic causes and the differentiated risk management of colorectal and associated malignancies require state-of-the-art management recommendations.

Regarding the identification of Lynch syndrome, the available criteria (revised Bethesda guidelines) appear to be effective for the selection of families for analysis of tumor MMR status. To date, the significant proportion of mutation carriers in Germany are still unknown and diagnosis still relies on patients with index cancers. Taking into account the tremendous importance the identification of MMR mutation carriers implies, future directives could include routine antibody staining for MMR genes in all CRCs. Increasing evidence suggests that microsatellite instability (MSI) and/or immunohistochemical (IHC) are an important prognostic factor and may predict the response to chemotherapy, therefore a broad application of these tools is envisaged in the near future.