The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients

Fariña-Sarasqueta, Arantza; Lijnschoten, Gesina van; Moerland, Elna; Creemers, G.J.; Lemmens, Valery; Rutten, H.J.T.; Brule, Adriaan J. C. van den

doi:10.1093/annonc/mdq258

Cited by 234 publications

(221 citation statements)

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“…KRAS mutations (codons 12, 13 and 61) were found in 35% of the patients in our study, consistent with other reports (6,8,24). We found a trend toward worse overall survival for KRAS-mutated tumors as compared with KRAS wt tumors.…”

Section: Krassupporting

confidence: 92%

“…MSI positivity was found in 23% of the patients, which is comparable with other subgroup analyses of recent studies reporting 15% to 25% MSI (6,8,23,24). Consistent with prior studies (25), MSI status was inversely correlated with the presence of the KRAS mutation.…”

Section: Msisupporting

confidence: 90%

“…The presence of the BRAF mutation varies more widely between recent studies (6% to 21%), and was 19% in our cohort (6,8,23,24). A recent meta-analysis found that the risk of mortality in colorectal cancer patients harboring the BRAF-V600E mutation is more than two times higher than those with wt BRAF (28).…”

Section: Brafmentioning

confidence: 55%

“…We found a trend toward worse overall survival for KRAS-mutated tumors as compared with KRAS wt tumors. In the prognostic setting, there are conflicts about the role of the KRAS mutational status (6,8,29). A recent large study of more than 1,000 colorectal cancers (stages I through IV) has shown that KRAS codon 12 mutation is associated with worse prognosis in BRAF wt colorectal cancers.…”

Section: Krasmentioning

confidence: 99%

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

Vogelaar

Erning

Reimers

et al. 2015

Mol Med

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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.

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Section: Krassupporting

confidence: 92%

Section: Msisupporting

confidence: 90%

Section: Brafmentioning

confidence: 55%

Section: Krasmentioning

confidence: 99%

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

Vogelaar

Erning

Reimers

et al. 2015

Mol Med

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“…4,[11][12][13][14][15] In fact, there is a lack of evidence regarding molecular factors that might predict responses to chemotherapy or sophisticatedly stratify prognoses in MSI-H colorectal cancer. 16 Although the BRAF V600E mutation has been thought to be related to a poor prognosis in colorectal cancer, 1,17 its prognostic effect was significant only in MSS colorectal cancer, not in MSI-H colorectal cancer. 18,19 In addition, the Beta2-microglobulin mutation, myosin 1A expression level, SMAD4 expression level and LINE-1 methylation level have been suggested to be associated with prognosis in patients with MSI-H colorectal cancer, [20][21][22][23][24] but more investigations are needed to establish molecular prognostic markers specific to MSI-H colorectal cancer.…”

mentioning

confidence: 99%

Expression status of wild-type HSP110 correlates with HSP110 T17 deletion size and patient prognosis in microsatellite-unstable colorectal cancer

Kim

Rhee

et al. 2014

Modern Pathology

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It has been recently suggested that the expression levels of mutant HSP110 could be a prognostic marker in colorectal cancer with a high level of microsatellite instability (MSI-H). The aim of our study was to validate the prognostic significance of HSP110 mutation using immunohistochemistry and DNA testing in MSI-H colorectal cancer. Wild-type HSP110 (HSP110wt)-specific immunohistochemistry was performed in 168 MSI-H colorectal cancer tissues, and their expression levels were evaluated using a four-tier scoring system (0/1 þ /2 þ /3 þ ). Of these tissues, 167 cases were analyzed for HSP110 T 17 deletion. Associations with clinicopathological, molecular and survival parameters were statistically analyzed. The low-level expression of HSP110wt (0/1 þ ) was observed in 40 MSI-H colorectal cancers (24%) and was significantly related to large HSP110 T 17 deletions (Z 4 bp, Po0.001). In survival analysis, patients with low HSP110wt expression (0/1 þ ) showed better diseasefree survival compared with those with high expression (2 þ /3 þ ; P ¼ 0.005). This significance in survival difference was maintained in patients with 5-fluorouracil-based chemotherapy-treated tumors (P ¼ 0.024) and in those with stage III/IV tumors (P ¼ 0.032). Multivariate analysis confirmed the role of HSP110wt expression as an independent prognostic factor (P ¼ 0.016, hazard ratio ¼ 4.32). In MSI-H colorectal cancer, a low expression of HSP110wt is associated with large HSP110 T 17 deletions and better clinical outcome. Immunohistochemistry of HSP110wt can be a simple and valuable tool for the prognostic and therapeutic stratification of patients with MSI-H colorectal cancer.

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Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer

et al. 2017

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The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients

Abstract: The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy.

Cited by 234 publications

References 19 publications

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

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

Expression status of wild-type HSP110 correlates with HSP110 T17 deletion size and patient prognosis in microsatellite-unstable colorectal cancer

Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer

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