Association between microsatellite instability status, clinicopathological features and mitochondrial DNA amplification in patients with colorectal cancer.

The relationship between BRAF-V600E mutations, mitochondrial DNA amplification and microsatellite instability-high (MSI-H) in colorectal cancer (CRC) has yet to be fully elucidated. The aim of the present study was to assess the association between the MSI status and BRAF-V600E gene mutations/clinicopathological features/mitochondrial DNA amplification in CRC. A non-interventional study analysis was performed using the clinicopathological features of 455 patients with CRC. Immunohistochemistry was used to evaluate four mismatch repair proteins (MutS homolog 2, MutS homolog 6, MutL homolog 1 and postmeiotic segregation increased 2), Ki-67 index, and programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) expression. Additionally, PCR coupled with capillary electrophoresis were used to ascertain the MSI status. Moreover, amplification refractory mutation system-PCR was used to detect BRAF-V600E gene mutation and fluorescence hybridization analysis was used to assess mitochondrial DNA. A total of 455 patients were divided into the MSI high (MSI-H) group (n=52) and microsatellite stability (MSS) group (n=403) based on their MSI status. Compared with the results of immunohistochemistry of four mismatch repair proteins, the consistency rate between mismatch repair protein deficiency and MSI was 94.23%. There were significant differences in PD-L1, primary tumor site, clinical stage, degree of differentiation, tumor size, lymph node metastasis and the occurrence of multiple primary tumors between the MSI-H group and MSS group (P<0.05 or P<0.001). However, there were no significant differences for sex, age, PD-1, Ki-67 expression and BRAF-V600E. The 24-60-month survival rate of the patients in the MSI-H group was significantly higher than that of those in the MSS group (P<0.05). Furthermore, the number of mitochondrial DNA was significantly amplified in the MSI-H group. In conclusion, the present study demonstrated that the combined detection of PD-L1 and MSI in patients with CRC can provide more accurate and effective guidance for personalized treatment.