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Langenbeck's Archives of Surgery

, Volume 399, Issue 1, pp 23–31 | Cite as

Clinical significance of microsatellite instability in colorectal cancer

  • Matthias KloorEmail author
  • Laura Staffa
  • Aysel Ahadova
  • Magnus von Knebel Doeberitz
Review Article

Abstract

Introduction

Colorectal cancer is a heterogeneous tumor type with regard to molecular pathogenesis and genetic instability. The majority of colorectal cancers display chromosomal instability and follow the classical adenoma-carcinoma sequence of tumor progression. A subset of about 15 % of colorectal cancers, however, displays DNA mismatch repair (MMR) deficiency and the high-level microsatellite instability (MSI-H) phenotype. MSI-H colorectal cancers can occur as sporadic tumors or in the context of hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome.

Clinical relevance

The MSI-H phenotype is a hallmark of Lynch syndrome-associated cancers, which is of diagnostic relevance for the identification of Lynch syndrome mutation carriers. MSI-H colorectal cancers are characterized by a distinct clinical behavior, which results from their particular molecular pathogenesis and gives microsatellite instability testing its clinical significance. The MSI-H phenotype shows association with proximal tumor localization, a dense local lymphocyte infiltration, and a low frequency of distant organ metastasis. Moreover, MSI-H colorectal cancers have a better prognosis than their microsatellite-stable counterparts. A distinct responsiveness of MSI-H colorectal cancer patients towards chemotherapy has been shown in several studies.

Conclusions

The clinical characteristics of MSI-H cancers are closely linked to their molecular pathogenesis, and research on the molecular alteration characteristic of MSI-H cancers may provide the basis for novel diagnostic or therapeutic approaches.

Keywords

Colorectal cancer Lynch syndrome Microsatellite instability Mismatch repair deficiency 

Notes

Acknowledgments

Work in the authors’ lab has been funded by grants of the Deutsche Krebshilfe (DKH, German Cancer Aid) and the Deutsche Forschungsgemeinschaft (DFG, German Cancer Research Foundation).

Conflicts of interest

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Matthias Kloor
    • 1
    • 2
    • 3
    • 4
    Email author
  • Laura Staffa
    • 1
    • 2
    • 3
  • Aysel Ahadova
    • 1
    • 2
    • 3
  • Magnus von Knebel Doeberitz
    • 1
    • 2
    • 3
  1. 1.Department of Applied Tumor Biology, Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Clinical Cooperation Unit Applied Tumor BiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Molecular Medicine Partnership Unit (MMPU)EMBLHeidelbergGermany
  4. 4.Abteilung für Angewandte Tumorbiologie Institut für PathologieUniversitätsklinikum HeidelbergHeidelbergGermany

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