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Papillary thyroid carcinoma prognosis worsened by high percentage of BRAF mutation
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High percentages of BRAFV600E alleles resulted in poorer outcomes among patients with papillary thyroid carcinoma, according to data published in The Journal of Clinical Endocrinology & Metabolism.
“In the present study, we examined the association between the percentage of BRAFV600E alleles and both the clinicopathological parameters and disease outcome in a large series of [papillary thyroid carcinomas], demonstrating that a high percentage of mutant BRAF alleles strongly predict a reduced disease-free survival,” the researchers wrote.
The study included 168 patients who underwent total thyroidectomy for papillary thyroid carcinoma at the Ospedale San Paolo and Fondazione IRCCS Ca’ Granda in Milan, Italy, between 1994 and 2010.
Patients were randomly and consecutively selected for genotyping for BRAFV600E alleles using BigDye Terminator sequencing and pyrosequencing, the researchers wrote.
They said BRAFV600E prevalence was higher when using pyrosequencing rather than BigDye Terminator sequencing (53.6% vs. 36.9%). In patients with papillary thyroid carcinoma who were positive for BRAFV600E alleles, the percentage of mutant alleles ranged from 5.1% to 44.7% of the total BRAF alleles (median, 20.6%).
BRAFV600E allele percentage related directly with age at diagnosis (P=.039) and tumor volume (P<.001), the researchers wrote.
According to the data, disease outcome was predicted by the following: percentage of BRAFV600E alleles (P=.014), tumor volume (P=.012) and lymph node metastasis (P=.008).
After a median of 5.1 years follow-up, disease recurred among 22.8% of patients. Recurrence was 2.1 times more frequent among BRAFV600E-positive patients compared with BRAFV600E-negative patients (33.3% vs. 15.6%; P=.04), the researchers wrote.
Perspective
Back to TopBarbara Burtness, MD
The Guerra article is notable for the finding that the proportion of cells in a papillary thyroid cancer with BRAF V600E alleles has prognostic importance. The authors undertook sequencing for BRAF mutation with 2 methodologies, and found significance with BigDye Terminator sequencing, which found fewer mutations than pyrosequencing did. Although they did not find an association between age, historically an important prognostic factor, and proportion of BRAF mutated alleles, the sample was only 168 patients, and there may have been inadequate power to examine this fully. The age of patients with >30% of mutated BRAF alleles was slightly higher. The rate of recurrence, at a median of 5 years of follow up for patients with >30% mutated BRAF alleles, was 40%, compared with 20% or lower for those with fewer or no mutated alleles.
The study has important implications for future studies of early stage papillary thyroid cancer, in which BRAF mutation allele proportion over 30% is now a putative risk factor for early recurrence.
Perspective
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Ralph Weichselbaum, MD
This paper demonstrates papillary thyroid cancer is a heterogeneous disease and that tumors with a preponderance of BRAFV600E have a worse outcome than tumors that contain a smaller percentage of BRAFV600E expressing cells. Therapies that target BRAFV600E may play a role in papillary thyroid cancer but are likely to require other therapeutic agents to address a heterogeneous tumor population.
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