V600E BRAF Mutations Indicate Poor Prognosis in NSCLC

Mutations more common in women, tied to more aggressive histotype in non-small-cell lung cancer

TUESDAY, Aug. 9 (HealthDay News) -- In patients with non-small-cell lung cancer (NSCLC), V600E BRAF mutations are more common in women and are associated with aggressive tumor histology and poor prognosis, according to a study published online Aug. 8 in the Journal of Clinical Oncology.

Antonio Marchetti, M.D., from the University-Foundation in Chieti, Italy, and colleagues examined the prevalence, distribution, and prognostic role of BRAF mutations in 1,046 white patients with NSCLC, of whom 739 had adenocarcinomas (ADCs) and 307 had squamous cell carcinomas (SCCs). Patients were analyzed for BRAF, KRAS, and EGFR mutations using high-resolution melting analysis followed by sequencing and strip hybridization assay.

The investigators found BRAF mutations in 36 (4.9 percent) of ADCs and one (0.3 percent) of SCCs. Of the BRAF mutations, 56.8 percent were V600E and 43.2 percent non-V600E. The prevalence of V600E-mutations was significantly higher in women than in men (8.6 versus 0.9 percent). Tumors with V600E mutations showed an aggressive histotype, distinguished by micropapillary histology in 80 percent of patients. V600E-mutated tumors were correlated with significantly reduced disease-free and overall survival rates (hazard ratio [HR], 2.67 and 2.97, respectively, in univariate analysis; HR, 2.19 and 2.18, respectively, in multivariate analysis). Non-V600E mutations were significantly associated with smoking and showed no correlation with clinicopathologic parameters or prognosis. Two tumors had BRAF and EGFR mutated concomitantly.

"V600E and non-V600E BRAF mutations affect different patients with NSCLC. V600E mutations are significantly associated with female sex and represent a negative prognostic factor. In addition, we identified a number of other clinicopathologic parameters potentially useful for the selection of patients carrying BRAF mutations," the authors write.

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Physician’s Briefing Staff

Physician’s Briefing Staff

Published on August 09, 2011

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