Microsatellite instability. A new predictive marker (?)

Microsatellite instability (MSI) is a hallmark of hereditary non-polyposis colorectal cancer (HNPCC), but also occurs in about 12%-15% of sporadic colorectal cancer (CRC) where it is a consequence of an epigenetic inactivation of MLH1. High frequency MSI (MSI-H; i.e. at least two of five specified m...

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Bibliographic Details
Published in:Der Pathologe 2010-10, Vol.31 Suppl 2, p.268
Main Author: Dietmaier, W
Format: Article
Language:ger
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Antimetabolites, Antineoplastic - therapeutic use
Biomarkers, Tumor - genetics
Chemotherapy, Adjuvant
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Colorectal Neoplasms, Hereditary Nonpolyposis - drug therapy
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
Colorectal Neoplasms, Hereditary Nonpolyposis - pathology
DNA Mismatch Repair - genetics
Drug Resistance, Neoplasm
Epigenesis, Genetic
Fluorouracil - therapeutic use
Humans
Microsatellite Instability
MutL Protein Homolog 1
Neoplasm Staging
Nuclear Proteins - genetics
Prognosis
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Summary:Microsatellite instability (MSI) is a hallmark of hereditary non-polyposis colorectal cancer (HNPCC), but also occurs in about 12%-15% of sporadic colorectal cancer (CRC) where it is a consequence of an epigenetic inactivation of MLH1. High frequency MSI (MSI-H; i.e. at least two of five specified microsatellite markers show instability) was shown in a large meta-analysis and in recent trials to be a positive prognostic marker for overall survival in CRC. MSI-H or mismatch repair deficiency (MMRD) was also shown to be a marker for ineffectiveness of adjuvant 5-fluorouracil (5-FU) based chemotherapy in CRC. At present, there are no guidelines defining the need for microsatellite analysis before chemotherapy. However, studies published to date provide data suggesting that MSI-H CRC patients should not receive adjuvant chemotherapy, with the exception of patients with other factors or poor prognosis (e.g. T4 tumors, G3/G4 status, blood or lymphatic vessel invasion). MSI or MMRD testing can contribute to a more individualized therapy of CRC and should be performed prior to planned 5-FU monotherapy or adjuvant chemotherapy in a non-metastatic setting.
ISSN:1432-1963
DOI:10.1007/s00292-010-1335-9