Prognostic Significance Of BRAF Mutations Research Articles

BRAF V600E mutation as a prognostic factor in cutaneous melanoma patients.

The prognostic significance of BRAF mutations in the natural course of melanoma is controversial. The aim of study was to assess the prognostic significance of BRAF V600E mutation in cutaneous melanoma patients. A total of 151 melanomas were included in the study. BRAF V600E mutation was detected using the real-time PCR. BRAF V600E mutation rate was 51%. BRAF mutation rate was higher for young patients (61.4%) and upper limbs (63.2%), trunk (59.3%) and head and neck (59.2%) were the most frequently afflicted sites in BRAF-mutant patients, whereas lower limbs were mostly affected in BRAF-wild patients (77.8%). Likewise, acral melanomas rarely harbored BRAF mutation (17.1%). The disease-free survivals regarding the entire and Stage III cohorts were longer in the BRAF-mutant group than in the BRAF-wild group (p = .006 and p = .004, respectively), whereas Stage I-II patients had no survival differences between BRAF statuses (p = .2). Likewise, BRAF-mutant patients had better overall survival (OS) time compared to BRAF-wild patients in all stages (p = .01), in Stage III (p = .01), and in Stage IV patients (p = .001). However, no differences between BRAF statuses were observed in Stage I-II melanomas (p = .3). In conclusion, BRAF V600E-mutant melanomas show favorable prognostic impact on both disease-free and OSs in all staged melanomas except local disease.

Prognostic significance of BRAF mutation alone and in combination with microsatellite instability in stage III colon cancer.

The prognostic significance of biomarkers in colorectal cancer is still being defined. This study aimed to determine the prognostic significance of BRAF mutation alone and in combination with microsatellite instability (MSI), in stage III colon cancer. Curatively resected stage III colon cancers were studied from a 33-year period. Clinicopathological data were collated (adjuvant chemotherapy, age, gender, obstruction, perforation, tumour location, grade, presence of mucin, nodal stage, extramural vascular, and perineural invasion). MSI status was established and molecular testing for BRAF (V600E) was performed. Four mutation categories were examined: "traditional" (microsatellite stable [MSS]/BRAF -ve), "presumed Lynch" (MSI/BRAF -ve), "sporadic MSI" (MSI/BRAF +ve), and "other BRAF" (MSS/BRAF +ve). These factors were correlated with cancer-specific survival. In total, 686 unselected cases met our inclusion criteria, of which 15.7% had a BRAF mutation and 13.8% showed MSI. In the adjusted analysis, neither BRAF mutation nor MSI mutation were independently prognostic. On univariate analysis, survival in presumed Lynch cancers was similar to traditional cancers (5-year survival: 62% and 61%, respectively). While there was no difference in cancer-specific survival between sporadic MSI and other BRAF, both these tumour group had poorer outcome when compared to traditional or presumed Lynch cancers. Adjusted analysis of the four groups, however, showed that none of the subgroups were independently prognostic. BRAF-mutated cancers demonstrated a trend toward poorer outcomes, however, when adjusted for clinicopathological factors and chemotherapy, BRAF mutation was not found to be an independent prognostic biomarker in stage III colon cancer, even when combined with MSI.

BRAF mutation marks out specific subgroups of glioma

Background: Molecular markers including isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion have been incorporated into the World Health Organization (WHO) 2016 classification of diffuse gliomas for integrated diagnostic reporting. The prognostic relevance of BRAF mutation among the newly established molecularly defined entities of gliomas remained relatively unexplored. Materials and Methods: We examined BRAF mutation in 578 adult diffuse gliomas and examined the clinical significance of the mutation in five histomolecular subgroups, namely oligodendrogliomas, IDH-mutant and 1p/19q-codeleted (Group I), astrocytomas, IDH- mutant (Group II), astrocytomas, IDH-wild-type (Group III), glioblastoma, IDH-mutant (Group IV), and glioblastoma, IDH-wild type (Group V). Results: Mutation rate of BRAF was 5.9% across the whole cohort and was 4.9%, 7.5%, and 7.0% in Group II, Group III, and Group V gliomas, respectively. Univariate analysis revealed a trend of poor overall survival in BRAF-mutant tumors among Group II gliomas, a trend which was also demonstrated by multivariable analysis. Among Group III and Group V gliomas, BRAF-mutant tumors seemed to exhibit more favorable survival in univariate analysis. Multivariable analysis further demonstrated the favorable prognostic significance of BRAF mutation in Group III (hazard ratio [HR] = 0.31, 95% confidence interval [CI] = 0.10–0.95, P = 0.04) and Group V gliomas (HR = 0.44, 95% CI = 0.18–1.09, P = 0.077). Conclusion: BRAF mutation appears to mark out a small subset of adult infiltrative gliomas with the distinct clinical outcome. Mutational analysis of BRAF can potentially contribute to the clinical risk stratification in the management of glioma patients in the context of the WHO 2016 classification.

Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status.

Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear. To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers. In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild-type (BRAFwt) melanoma at the time of first distant metastasis. In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P=0·01) and significantly higher (P=0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P<0·01). In BRAFm melanoma, elevated S100B levels showed no prognostic influence (P=0·18). Elevated lactate dehydrogenase (LDH) levels had a significantly negative impact on mOS in both groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared with BRAFm patients not receiving BRAFi (P=0·01). No difference in mOS between BRAFm patients who did not receive BRAFi treatment and BRAFwt patients was observed. Better mOS was observed in BRAFm patients treated with BRAFi. BRAFm patients not treated with BRAFi show similar survival curves to BRAFwt patients. Elevated LDH is a BRAF-independent prognostic parameter; S100B has prognostic significance in BRAFwt melanoma only.

1147 - BRAF Mutations Are Frequent in Malignant Melanoma in Israeli Population and Predicts Poor Response to Biochemotherapy

ABSTRACT Introduction Malignant melanoma is a highly-aggressive form of skin cancer. Lesions developing in non-chronically sun-damaged skin are associated with frequent activating mutations in BRAF with substitution of valine for glutamic acid at position 600 (BRAFV600E). The prognostic significance of BRAF mutation in patients with metastatic melanoma (MM) treated with chemobiotherapy is uncertain. Patients and methods We studied the prognostic significance of BRAF mutation in 69 patients with MM treated with chemobiotherapy at the Soroka Medical Center, Beer Chemobiotherapy consisted of BCNU, DTIC, cisplatin, IL-2, alpha-interferon, GM-CSF, cimetidine, and tamoxifen. Samples were micro-dissected at the molecular lab, Hacarmel hospital, and subjected to high-resolution melting analysis using primers flanking codon 600 in the BRAF gene. All abnormal high-resolution melting traces were subjected to bidirectional DNA sequencing. Results Mean age-55 years (range 25-80); Gender-male/female–41/28; Ulceration–30/54; Site of primary lesion: limbs/head/neck/trunk/retina/mucous membranes–12/13/0/14/2/3; Depth: T1/T2/T3/T4/undetermined-3/8/24/16/4; Lymph node biopsy–32/54; Lymph node involvement: none/micrometastases/metastases–14/2/16. BRAF mutation–42/69 (61%). BRAF mutation correlated with poor response to treatment (P = 0.056), but had no effect on disease-free interval (DFI). DFI was affected only by nodal stage (P = 0.026). In Cox multivariate analysis only male gender was associated with worse prognosis (P = 0.03), while BRAF mutation showed a trend towards worse prognosis (P = 0.169). Conclusions BRAF mutation in patients with MM treated with chemobiotherapy may predict poor response to treatment. Disclosure All authors have declared no conflicts of interest.

Is It Good or Bad to Find a BRAF Mutation?

Is It Good or Bad to Find a <i>BRAF</i> Mutation?