A prospective study to assess the clinicopathological and prognostic value of BRAF V600E mutation in metastatic colorectal cancer

Introduction: BRAF is a protein kinase downstream of RAS in the RAS-RAF-MEK-ERK kinase pathway, the prevalence of BRAF mutation might be underestimated, while it is considered a major negative prognostic marker and is associated with resistance to standard chemotherapeutic regimens in metastatic colorectal cancer (mCRC) patients, justifying a personalized therapeutic approach in BRAF-mutated mCRC patients. Given this poor outcome in patients with BRAF-mutated mCRC, optimizing therapy is an important goal. Objectives: This study aimed to study BRAF mutation in patients with metastatic CRC and its association with clinicopathological factors and survival outcomes. Patients and Methods: This prospective study included 55 patients with histologically proven CRC with metastatic disease, either radiologically or pathologically proven. BRAFV600E mutation analysis was performed using the polymerase chain reaction (PCR) and reverse hybridization method on formalin-fixed and paraffin-embedded extracted DNA samples. Results: In our study, 55 patients were enrolled. The mean age was 49.5 years with male predominance. Among patients enrolled in the study, 54 were evaluated for survival over one year. The median progression-free survival (PFS) was 11.167 months, and the median overall survival (OS) was 34.5 months. BRAF V600E mutation was detected in 9.1% of patients and all of them presented with synchronous metastasis, with statistical significance (P = 0.0339). No significant difference was observed in clinicopathological factors, PFS, or OS between BRAF-mutant and wild-type patients. Only 48 patients were evaluated for their response to first-line therapy; it was found that most patients who did not receive targeted therapy had progressive disease with a statistical significance of P = 0.0450. A median PFS of 19.2 months was also noted with statistical significance (P = 0.0121). Conclusion: The BRAFV600E mutation is associated with more aggressive features, but no association with PFS or OS was found. Chemotherapy with the addition of targeted therapy has an impact on PFS. Further investigations are therefore warranted and the inclusion of BRAF-mutated mCRC patients in clinical trials needs to be encouraged.