The Relationship between Microsatellite Instability and KRAS Mutations in Liver-metastatic Colorectal Cancer: A Preliminary Cross-sectional Study

Abstract

Background: Colorectal cancer (CRC) has a high mortality rate due to the development of liver metastases. Mutations in RAS and mismatch repair (MMR) genes are common in CRC, with Kirsten rat sarcoma viral oncogene (KRAS) mutations occurring in approximately 44% of cases and MSI in 15%. Both mutations are associated with poor prognosis. The study aims to identify MSI status and KRAS mutations in liver-metastatic CRC at a hospital in eastern Indonesia.

Methods: In this cross-sectional study, 57 patients with liver-metastatic CRC were included. We evaluated KRAS mutations and microsatellite instability (MSI) status in patients’ DNA extracted from paraffin blocks. The procedures involved included specimen examination, DNA extraction, and genetic sequencing. The data were analyzed using SPSS version 25.0. Fisher’s exact test was utilized to evaluate the relationship between MSI status and KRAS mutations. A significance level of p<0.05 was considered statistically significant.

Results: This study included patients aged 16–80 years with liver-metastatic colon cancer. Patients were primarily male with left-sided tumors of adenocarcinomatous histopathology and high histopathological grade. Of the 57 subjects, 31.6% had MSI-high (MSI-H) tumors and 21.1% expressed mutant KRAS. The majority of MSI-H tumors (82% of patients) expressed mutant KRAS, while most MSI-low (MSI-L) tumors (60% of patients) expressed wild-type KRAS. However, Fisher’s exact test indicated no significant relationship between MSI status and KRAS mutation status in liver-metastatic colon cancer (p = 0.489).

Conclusions: This study found no significant relationship between MSI status and KRAS mutation status in patients with liver-metastatic colon cancer.