The Prognostic Value of Microsatellite Instability, KRAS, BRAF and PIK3CA Mutations in Stage II Colon Cancer Patients

Abstract

In the era of personalized cancer medicine, identifying mutations within patient tumors plays an important role in defining highrisk stage II colon cancer patients. The prognostic role of BRAF V600E mutation, microsatellite instability (MSI) status, KRAS mutation and PIK3CA mutation in stage II colon cancer patients is not settled. We retrospectively analyzed 186 patients with stage II colon cancer who underwent an oncological resection but were not treated with adjuvant chemotherapy. KRAS mutations, PIK3CA mutation, V600E BRAF mutation and MSI status were determined. Survival analyses were performed. Mutations were found in the patients with each mutation in the following percentages: 23% (MSI), 35% (KRAS), 19% (BRAF) and 11% (PIK3CA). A trend toward worse overall survival (OS) was seen in patients with an MSI (5-year OS 74% versus 82%, adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6-4.9) and a KRAS-mutated tumor (5-year OS 77% versus 82%, adjusted HR 1.7, 95% CI 0.8-3.5). MSI and BRAF-mutated tumors tended to correlate with poorer disease-free survival (DFS) (5-year DFS 60% versus 78%, adjusted HR 1.6, 95% CI 0.5-2.1 and 5-year DFS 57% versus 77%, adjusted HR 1.1, 95% CI 0.4-2.6 respectively). In stage II colon cancer patients not treated with adjuvant chemotherapy, BRAF mutation and MSI status both tended to have a negative prognostic effect on disease-free survival. KRAS and MSI status also tended to be correlated with worse overall survival.

The Prognostic Yield of Biomarkers Harvested in Chemotherapy-Naive stage II Colon Cancer: Can We Separate the Wheat from the Chaff?

“…This contradictory finding obviously warrants explanation based on the background of existing literature from the past couple of decades. Vogelaar et al also confirmed a trend toward poorer prognosis in patients with mutant KRAS or BRAF (12). The negative impact of these mutations has been noted by others in both early-and late-stage colorectal cancer (CRC) (11,(14)(15)(16).…”

“…In a recent study, in this journal (12), the role of MSI, KRAS, BRAF and PIK3CA in stage II colon cancers was investigated. In the study by Vogelaar et al (12), MSI was found in 23% of patients with a trend toward reduced disease-free and overall survival for patients with MSI, which is in contrast to the prognostic role of MSI found by others in early-stage colon cancers (13).…”

Prognostic and predictive role of DNA mismatch repair status in stage II‐III colorectal cancer: A systematic review and meta‐analysis

“…Sample sizes of the selected studies ranged from 32 to 2693 (median, 266). Among these studies, 21 studies were conducted in Europe, 12 studies in Asia, 6 studies in America, 3 studies in Australia, and the remaining 9 studies were multicenter studies . Twenty‐seven studies were specifically restricted to patients with colon cancer, while other 24 studies investigated patients with colorectal cancer.…”

“…Sample sizes of the selected studies ranged from 32 to 2693 (median, 266). Among these studies, 21 studies were conducted in Europe, 6,17,[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] 12 studies in Asia, [49][50][51][52][53][54][55][56][57][58][59][60] 6 studies in America, 16,[61][62][63][64][65] 3 studies in Australia, [66][67][68] and the remaining 9 studies were multicenter studies. [69][70][71][72][73][74][75][76]…”

¿Existen ventajas clínicas al evaluar el estado de los genes KRAS, NRAS, BRAF, PIK3CA, PTEN y HER2 en pacientes con cáncer colorrectal?

“…La mutación del gen KRAS se comporta como un factor pronóstico negativo para la supervivencia global en el cáncer rectal y para la supervivencia libre de enfermedad en el cáncer de colon en estadio clínico II [87][88][89] ; de la misma manera, la mutación en el BRAF tiene un efecto pronóstico negativo en la supervivencia global en el estadio clínico II 90,91 . Las mutaciones en los genes KRAS y BRAF se asocian significativamente con la supervivencia libre de enfermedad y la supervivencia global más corta en pacientes con tumores de microsatélites estables, pero no en pacientes con tumores con inestabilidad de microsatélites 92 .…”