Difference Between Proximal and Distal Microsatellite-Unstable Sporadic Colorectal Cancers: Analysis of Clinicopathological and Molecular Features and Prognoses

Distal microsatellite instability (MSI)-high colorectal cancers (CRCs) have been investigated by few studies and are generally regarded as having similar features to proximal MSI-high CRCs. In the present study, we aimed to elucidate whether distal sporadic MSI-high CRCs displayed distinguished clinicopathological and molecular features from proximal MSI-high CRCs. All patients who underwent their first surgical resections for stage I-IV sporadic CRCs between August 2003 and August 2006 were initially considered for enrolment, and their MSI data were prospectively collected. Among them, 135 patients with MSI-high CRCs (86 proximal and 49 distal CRCs) were finally identified. The clinicopathological and molecular characteristics, and prognosis of these cases with MSI-high CRCs were reviewed and compared according to tumor site (proximal versus distal). Distal MSI-high CRCs showed significantly more frequent association with younger age, male gender, differentiated histology, small tumor size, distant metastasis, stability in BAT25 and BAT26, and hMLH1 expression on immunohistochemical staining as compared with proximal MSI-high CRCs. In addition, distal MSI-high CRCs demonstrated significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (87.0% versus 97.4%; 81.6% versus 95.9%). For stage III-IV CRCs, distal MSI-high CRCs also showed significantly worse 3-year overall and disease-free survival rates than proximal MSI-high CRCs (72.2% vs. 90.5%; 58.3% vs. 94.4%). These results indicated that distal sporadic MSI-high CRCs formed a distinct subgroup with distinguished clinicopathological and molecular features from proximal MSI-high CRCs. In addition, this study demonstrated that distal MSI-high CRCs had worse prognosis than proximal MSI-high CRCs.