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BRAF-mutated microsatellite-stable adenocarcinoma of the proximal colon

Monday 13 February 2012

The association of BRAF V600E mutation and the presence of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) often confound analysis of BRAF mutation status and survival in colorectal carcinoma.

Compared with BRAF wild-type adenocarcinomas, BRAF-mutated adenocarcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (80% vs. 47%; P=0.008), mean number of lymph node metastases (4.5 vs. 2.2; P=0.01), perineural invasion (40% vs. 8%; P=0.0004), and high tumor budding (80% vs. 52%; P=0.02). (22314188)

BRAF-mutated adenocarcinomas frequently contained areas with mucinous histology (P=0.0002) and signet ring histology (P=0.03), compared with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas. (22314188)

Patients with BRAF-mutated adenocarcinomas had a median survival of 12.3 months with a 1-year probability of survival of 54% and a 1-year disease-free survival of 56%. Patients with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas had significantly improved overall survival and disease-free survival compared with patients with BRAF-mutated adenocarcinomas. (22314188)

When adjusting for tumor stage, survival analysis demonstrated that patients with BRAF-mutated adenocarcinoma had a significantly poor overall survival and disease-free survival (hazard ratios 6.63, 95% CI, 2.60-16.94; and 6.08, 95% CI, 2.11-17.56, respectively) compared with patients with KRAS/BRAF wild-type adenocarcinomas. (22314188)

No significant difference in overall or disease-free survival was identified between patients with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas. (22314188)

BRAF-mutated proximal colon adenocarcinomas with proficient DNA mismatch repair have a dismal prognosis with an aggressive clinical course and often display mucinous differentiation, focal signet ring histology, and other adverse histologic features such as lymphatic and perineural invasion and high tumor budding. (22314188)

References

- BRAF-mutated, Microsatellite-stable Adenocarcinoma of the Proximal Colon: An Aggressive Adenocarcinoma With Poor Survival, Mucinous Differentiation, and Adverse Morphologic Features. Pai RK, Jayachandran P, Koong AC, Chang DT, Kwok S, Ma L, Arber DA, Balise RR, Tubbs RR, Shadrach B, Pai RK. Am J Surg Pathol. 2012 Feb 3. PMID: 22314188