BRAF V600E 돌연변이 진행성 직결장암 환자들의 임상 및 병리학적 특성

Abstract

Background and Objectives: BRAF-mutated colorectal cancers are known to have a poor prognosis and low response to current chemotherapy. The response of BRAF-mutant patients to treatment was heterogeneous, suggesting that other mechanisms may be involved in the prognosis within BRAF V600E mutant colorectal cancers. We analyzed the clinicopathological characteristics of Korean patients with BRAF-mutant metastatic or recurrent colorectal cancer. Material and Methods: Between January 2005 and October 2015, data of patients with metastatic or recurrent colorectal cancer who underwent BRAF mutation testing at the Asan Medical Center were reviewed retrospectively. The clinicopathological characteristics and survival of patients with BRAF mutated tumors were compared with those of patients with BRAF wild-type tumors. Among the patients with BRAF-mutated tumors, pathological analysis was performed on cases displaying extreme phenotypes. Results: A total of 2,311 patients were included in the analysis. We detected BRAF mutations in 124 (5.4%) patients. BRAF-mutated tumors were frequently right-sided (47.6%), and BRAF-mutant patients were more likely to have mismatch repair (MMR)-deficient tumors (p = 0.011), poorly differentiated histology (p < 0.001), and metastatic disease at diagnosis (p < 0.001). The median follow-up duration was 25.9 months, and median overall survival (OS) was 14.6 months (95% CI, 11.7–17.5) for patients with BRAF-mutated tumors and 31.5 months for patients with BRAF wild-type tumors (95% CI, 29.9 – 33.2, p < 0.001). The median progression-free survival (PFS) was 5.70 months (95% CI, 4.16–7.24) for patients with BRAF-mutated tumors, compared to 9.61 months (95% CI, 9.20–10.02) for patients with BRAF wild-type tumors (p < 0.001). Among the patients with BRAF-mutated tumors, 12 patients survived longer than 30 months. Cases with good prognosis were more likely to have acellular mucin pools (p = 0.002), lymphoplasmacytic infiltration (p = 0.025), and Crohn-like lymphoid aggregates (p = 0.007). Patients in the poor prognosis group (OS less than 6 months) were more likely to display aggressive features such as poorly differentiated carcinomas (p = 0.033), lymphovascular invasion (p < 0.001), serosal exposure (p = 0.044), and tumor necrosis (p = 0.006). Conclusions: Clinical outcomes for patients with BRAF-mutated colorectal cancer in real clinical practice were poor in terms of OS and PFS. However, a small proportion of patients survived longer than 30 months, which was comparable to the survival duration of wild-type BRAF colorectal cancer patients. This population showed unique pathological characteristics, which need to be validated.