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. 2010 Dec;17(12):3370-8.
doi: 10.1245/s10434-010-1147-4. Epub 2010 Aug 12.

Improved testing for microsatellite instability in colorectal cancer using a simplified 3-marker assay

Iyare Esemuede  1 , Ann Forslund, Sajid A Khan, Li-Xuan Qin, Mark I Gimbel, Garrett M Nash, Zhaoshi Zeng, Shoshana Rosenberg, Jinru Shia, Francis Barany, Philip B Paty
Affiliations

Improved testing for microsatellite instability in colorectal cancer using a simplified 3-marker assay

Iyare Esemuede et al. Ann Surg Oncol. 2010 Dec.

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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Figures

FIG. 1
FIG. 1
Chromosomal arm losses and gains as determined by CGH analysis (see methods) is shown for 3 groups of primary colorectal cancers: true MSI cancers (16 cases) for which the 3-marker MSI test was positive, putative MSI cancers (4 cases) for which the NCI 5-marker test was positive but the 3-marker test was negative, and MSS cancers (5 cases). Chromosomal arm gain is shown in black; arm loss is shown in white
FIG. 2
FIG. 2
Disease-specific survival is shown for true MSI colorectal cancers (positive on 3-marker test), false MSI cancers (positive on NCI 5-marker test but negative on 3-marker test), and MSS cancers. True MSI cancers have favorable prognosis compared with the other groups (P < .01)
See this image and copyright information in PMC

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