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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2010

01-12-2010 | Translational Research and Biomarkers

Improved Testing for Microsatellite Instability in Colorectal Cancer Using a Simplified 3-Marker Assay

Authors: Iyare Esemuede, MD, Ann Forslund, PhD, Sajid A. Khan, MD, Li-Xuan Qin, PhD, Mark I. Gimbel, MD, Garrett M. Nash, MD, Zhaoshi Zeng, MD, Shoshana Rosenberg, MS, Jinru Shia, MD, Francis Barany, PhD, Philip B. Paty, MD

Published in: Annals of Surgical Oncology | Issue 12/2010

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Abstract

Background

In colorectal cancer (CRC), microsatellite instability (MSI) is a valuable marker of defective DNA mismatch repair that identifies cancers with distinct phenotypic properties, including favorable survival. However, the optimal assay for MSI status is unknown. We have evaluated a simplified 3-marker assay for MSI and compared it with the 5-marker (NCI) assay to see if technical variations in MSI testing are important.

Materials and Methods

DNA samples from 357 CRCs were evaluated for MSI using the 5 microsatellite markers recommended for the NCI assay (BAT 25, BAT26, D2S123, D5S346, and D17S250). Results were compared with a simplified 3-marker assay (BAT25, BAT26, and D2S123). CRCs identified as MSI were evaluated for their clinical, pathological, and genetic characteristics.

Results

The 5-marker assay identified 96 cancers as MSI. Only 56 of these were MSI by the 3-marker assay (3-marker+ group), leaving 40 cases identified as MSI only by NCI criteria (3-marker− group). The remaining 261 cancers were microsatellite stable (MSS). The 3-marker+ MSI tumors had features characteristic of MSI tumors: more proximal, poorly differentiated, associated with hereditary nonpolyposis colorectal cancer (HNPCC), more BRAF mutations, fewer KRAS mutations, better 5-year disease-specific survival, more frequent mismatch repair (MMR) protein loss, and less likely to be metastatic on presentation (P < .05). Chromosomal arm loss was observed only in 3-marker− MSI and MSS cancers (P < .05).

Conclusion

The 3-marker MSI assay outperforms the traditional 5-marker assay for identifying patients with favorable prognosis and homogeneous clinical and genetic features. More accurate MSI testing should improve prognostic and predictive scoring systems for colorectal cancer.
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Metadata
Title
Improved Testing for Microsatellite Instability in Colorectal Cancer Using a Simplified 3-Marker Assay
Authors
Iyare Esemuede, MD
Ann Forslund, PhD
Sajid A. Khan, MD
Li-Xuan Qin, PhD
Mark I. Gimbel, MD
Garrett M. Nash, MD
Zhaoshi Zeng, MD
Shoshana Rosenberg, MS
Jinru Shia, MD
Francis Barany, PhD
Philip B. Paty, MD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1147-4

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