Blaker H, et al. - During this study, authors gauged the stage-specific prognostic value of combined testing for microsatellite instability (MSI-H) and BRAF for patients with colorectal cancer (CRC) at 22 hospitals in Germany, between 2003 and 2010. BRAF mutations reduced the survival of patients in stage III or IV (but not stage II) tumors with microsatellite stability (MSS) in the assessment of approximately 2,000 patients with CRC. Yielded data recommended against the testing of stage I or II colorectal tumors for BRAF mutations.

Methods

• This retrospective analysis examined colorectal tumor samples collected from 1,995 patients at 22 hospitals in Germany between 2003 and 2010.
• Using an established mononucleotide marker panel, the samples were assessed for MSI-H.
• BRAF mutations (BRAF600E) were detected by Sanger sequencing or in tissue microarray blocks using immunohistochemistry.
• Cancers were categorized as having MSS without mutations in BRAF, MSS with mutant BRAF, MSI-H without mutations in BRAF, and MSI-H with mutant BRAF.
• The link between tumor categories with clinical and pathological features and patient’s overall, disease-specific, and recurrence-free survival (median follow-up time, 5.1 years) was scrutinized.

Results

• Yielded data displayed that tumors were stage I in 364 (18%), stage II in 678 (34%), stage III in 673 (34%) and stage IV (14%) in 280 patients.
• The location of 63% of tumors was found in the colon and 37% in the rectum.
• Most tumors (85%) reported MSS without mutations in BRAF, 3% had MSS with mutant BRAF, 7% had MSI-H without mutations in BRAF, and 5% had MSI-H with mutant BRAF.
• In patients whose tumors were MSI-H, mutation of BRAF did not exert a notable impact on the survival time.
• Patients whose tumors had MSS with mutant BRAF exhibited a marked reduction in the overall survival (hazard ratio [HR], 2.16; 95%CI, 1.54-3.04; P < .001), disease-specific survival (HR, 2.59; 95%CI, 1.77-3.79; P < .001), and recurrence-free survival (HR, 2.45; 95%CI, 1.70-3.52; P < .001) compared to subjects whose tumors had MSS without BRAF mutation.
• Despite the correlation between BRAF mutations in tumors with MSS with disease-specific survival of patients with stage III or IV tumors, (P < .001); these features did not influence the survival of patients with stage II tumors (P=.639).