The aims of this study were to molecularly characterize tumors from disease stage II and III colorectal cancer (CRC) patients with regard to BRAF, PIK3CA, KRAS mutations and microsatellite instability (MSI) status, and to compare the frequency of the mutations in patients stratified by disease recurrences.
Material and methods
BRAF, PIK3CA, KRAS mutations and MSI status were analyzed in fresh frozen tumors from patients with CRC. The analyzed tissue was selected from curatively treated patients with disease stage II and III. These patients were stratified for disease recurrence; stage II without recurrence (n=19) and with recurrence (n=18) and stage III without recurrence (n=17) and stage III with recurrence (n=19).
No major difference in frequency of mutations in BRAF, KRAS, PIK3CA and MSI was demonstrated between patients with or without recurrence or disease stages II-III. Occurrence of any of the analyzed mutations (BRAF, KRAS and PIKC3A) was more frequent when the tumor was localized in the colon (98%) versus the rectum (2%) (p=0.015). MSI tumors demonstrated a high frequency of BRAF mutations (63%) and a low frequency of KRAS mutations (1%). Tumors of patients without recurrence revealed higher frequency of MSI (p=0.038). BRAF mutations were more abundant in patients with stage III disease without recurrence (n=7) compared to stage III patients with recurrence (n=2). Patients with stage III disease and BRAF mutation had a better cancer specific survival, compared with patients in stage III without BRAF mutation (p=0.043).
The results indicate that patients with CRC stage III without recurrence have a higher frequency of BRAF mutation compared to stage III patients with recurrence, moreover those patients with stage III disease and BRAF mutation have better prognosis than those with stage III disease and no BRAF mutation.