Location-related differences in sporadic microsatellite unstable colorectal cancer

Abstract

Background Microsatellite unstable CRC is associated with female gender, large tumours, and poor differentiation. However, there are few reports about the characteristics and differences of sporadic microsatellite unstable CRC based on tumour location. Aims Site-specific heterogeneity of sporadic microsatellite unstable colorectal cancer (CRC) based on location was elucidated. Methods We enrolled 164 CRC patients with high-frequency microsatellite instability (MSI-H) from the prospective database of 2686 consecutive CRC patients who underwent surgical resection. We analysed microsatellite instability (MSI) and expression of mismatch repair (MMR) proteins (MLH1, MSH2, and MSH6). Results Among the 164 MSI-H CRC, 105 (64.0%) were located in the proximal colon and 59 (36.0%) were located in the distal colon. The proximal MSI-H CRC was predominantly in female ( p = 0.014), had a more aggressive differentiation ( p = 0.001), was of advanced stage ( p = 0.035), and had a frequent loss of MLH1 expression ( p = 0.005) compared to the distal MSI-H CRC. Conclusion There were different clinicopathologic characteristics and MMR protein expression between proximal and distal MSI-H CRC. These findings suggest that the underlying carcinogenic pathway or molecular background differs according to location, despite being microsatellite unstable CRC.