Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer

Although microsatellite instability-high (MSI-H) colorectal cancers (CRCs) have been shown to exhibit a distinct phenotype, the clinical value of MSI-low (MSI-L) in CRC remains unclear. We designed this study to examine the clinicopathologic characteristics and oncologic implications associated with MSI-L CRCs. We retrospectively reviewed data of CRC patients from 3 tertiary referral hospitals in Korea, who underwent surgical resection between January 2003 and December 2009 and had available MSI testing results. MSI testing was performed using the pentaplex Bethesda panel. Clinicopathologic features and oncologic outcomes were compared between MSI-L and microsatellite stable (MSS) CRCs; prognostic factors for survival were also examined. Of the 3019 patients reviewed, 2621 (86.8%) were MSS, and 200 (6.6%) were MSI-L; the remaining 198 (6.6%) were MSI-H. MSI-L and MSS CRCs were comparable in terms of their clinicopathologic features, with the exception of proximal tumor location (MSI-L 30.0% vs MSS 22.1%, P = 0.024) and tumor size (MSI-L 5.2 ± 2.6  cm vs MSS 4.6 ± 2.1  cm, P = 0.001). No differences were detected in either 3-year disease-free survival (MSI-L 87.2% vs MSS 82.6%, P = 0.121) or 5-year overall survival (OS) (MSI-L 74.2% vs MSS 78.3%, P = 0.131) by univariable analysis. However, MSI-L was an independent prognostic factor for poor OS by Cox regression analysis (hazard ratio 1.358, 95% confidence interval 1.014-1.819, P = 0.040). MSI-L may be an independent prognostic factor for OS in sporadic CRCs despite their clinicopathologic similarity to MSS. Further studies investigating the significance of MSI-L in the genesis and prognosis of CRCs are needed.