Investigating BRAF gene mutation with the incidence of MSI (Micro Satellite Instability) in patients with colorectal cancer and comparing it with the pathological findings of these patients in surgical samples

Abstract

Somatic point mutations in the BRAF gene disrupt the MAP kinase cycle, interfering with normal cell proliferation and survival programs. Therefore, investigating BRAF gene mutations is crucial for diagnosing the disease and selecting appropriate treatments using BRAF inhibitors. Additionally, around 15% of colorectal cancers result from defects in mismatch repair. Tumors that are MSI-positive respond differently to 5-fluorouracil and other chemotherapy drugs. Understanding this can provide insights into how this defect influences the severity, extent, and pathological involvement of the tumor, while also improving our knowledge of the prognosis and enabling more tailored therapeutic advances. Methods: In this retrospective study, surgical samples from patients with colorectal cancer over the past five years were collected and transferred, under cold chain preservation, to one of the laboratories in East Azerbaijan Province for assessment of BRAF mutations and Microsatellite Instability (MSI) using IHC staining. The obtained data were compared with the pathological results of these patients' surgical samples, focusing on tumor differentiation, depth of invasion, and the number of involved lymph nodes. The study also considered patient age and gender. A total of 282 samples were collected. It should be noted that paraffin-embedded blocks from patients, previously used for pathology reports, were employed for BRAF mutation analysis via PCR and MSI assessment through immunohistochemistry staining, without any new sampling from the patients. Results: The MSI mutation rate in colorectal cancer patients was 18.4%, and the BRAF mutation rate was 12.4%. Among colorectal cancer patients with MSI instability, the BRAF mutation rate was 30.8%. The prognosis for patients with simultaneous BRAF and MSI mutations was worse compared to patients without these mutations or those with MSI alone. The depth of colon cancer invasion was greater in patients with BRAF mutations compared to those without this genetic mutation.