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Current Treatment Options in Oncology
Published in: Current Treatment Options in Oncology 7/2015

01-07-2015 | Lower Gastrointestinal Cancers (AB Benson, Section Editor)

Microsatellite Instability Testing and Its Role in the Management of Colorectal Cancer

Authors: Hisato Kawakami, MD, PhD, Aziz Zaanan, MD, Frank A. Sinicrope, MD

Published in: Current Treatment Options in Oncology | Issue 7/2015

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Opinion statement

TNM stage remains the key determinant of patient prognosis after surgical resection of colorectal cancer (CRC), and informs treatment decisions. However, there is considerable stage-independent variability in clinical outcome that is likely due to molecular heterogeneity. This variability underscores the need for robust prognostic and predictive biomarkers to guide therapeutic decision-making including the use of adjuvant chemotherapy. Although the majority of CRCs develop via a chromosomal instability pathway, approximately 12–15 % have deficient DNA mismatch repair (dMMR) which is characterized in the tumor by microsatellite instability (MSI). Tumors with the dMMR/MSI develop from a germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2), i.e., Lynch syndrome, or more commonly from epigenetic inactivation of MLH1 MMR gene. CRCs with dMMR/MSI status have a distinct phenotype that includes predilection for the proximal colon, poor differentiation, and abundant tumor-infiltrating lymphocytes. Consistent data indicate that these tumors have a better stage-adjusted survival compared to proficient MMR or microsatellite stable (MSS) tumors and may respond differently to 5-fluorouracil-based adjuvant chemotherapy. To increase the identification of dMMR/MSI patients in clinical practice that includes those with Lynch syndrome, it is recommended that all resected CRCs to be analyzed for MMR status. Available data indicate that patients with stage II dMMR CRCs have an excellent prognosis and do not benefit from 5-fluorouracil (FU)-based adjuvant chemotherapy which supports their recommended management by surgery alone. In contrast, the benefit of standard adjuvant chemotherapy with the FOLFOX regiment in stage III dMMR CRC patients awaits further study and therefore, all patients should be treated with standard adjuvant FOLFOX.
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Metadata
Title
Microsatellite Instability Testing and Its Role in the Management of Colorectal Cancer
Authors
Hisato Kawakami, MD, PhD
Aziz Zaanan, MD
Frank A. Sinicrope, MD
Publication date
01-07-2015
Publisher
Springer US
Published in
Current Treatment Options in Oncology / Issue 7/2015
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-015-0348-2

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