title: Low-Level Microsatellite Instability as a Potential Prognostic Factor in Sporadic Colorectal Cancer.
abstract: 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.
authors.affiliation: From the Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun (SYL); Department of Surgery, Seoul National University Bundang Hospital, Seongnam (D-WK, MHI, H-KO, S-BK); Korean Hereditary Tumor Registry, Seoul National University College of Medicine, Seoul (D-WK); Department of Pathology, Seoul National University Bundang Hospital, Seongnam (HSL); Department of Surgery, Severance Hospital, Yonsei University College of Medicine (BSM, WRK, KYL, NKK); and Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (JWH, J-AY, WYL, HCK).
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Myong Hoon
authors.initials: MH
authors.lastname: Ihn
authors.forename: Heung-Kwon
authors.initials: HK
authors.lastname: Oh
authors.forename: Byung Soh
authors.initials: BS
authors.lastname: Min
authors.forename: Woo Ram
authors.initials: WR
authors.lastname: Kim
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Huh
authors.forename: Jung-A
authors.initials: JA
authors.lastname: Yun
authors.forename: Kang Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Nam Kyu
authors.initials: NK
authors.lastname: Kim
authors.forename: Woo Yong
authors.initials: WY
authors.lastname: Lee
authors.forename: Hee Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D056910:Republic of Korea; D012189:Retrospective Studies; D016019:Survival Analysis