TY - JOUR
T1 - A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome
AU - Guerra, Anna
AU - Fugazzola, Laura
AU - Marotta, Vincenzo
AU - Cirillo, Massimo
AU - Rossi, Stefania
AU - Cirello, Valentina
AU - Forno, Irene
AU - Moccia, Tania
AU - Budillon, Alfredo
AU - Vitale, Mario
PY - 2012/7
Y1 - 2012/7
N2 - Context: BRAFV600E is considered a negative prognostic marker in papillary thyroid carcinoma (PTC), but unexplained conflicting results are present in the literature. In light of the new finding that most PTC consist of a mixture of tumor cells with wild-type and mutant BRAF, we examined the associations between the percentage of BRAFV600E alleles and both the clinicopathological parameters at time of diagnosis and the disease outcome in a large series of PTCs. Study Design: Tumors from 168 patients with PTC were genotyped for BRAFV600E using BigDye Terminator sequencing and pyrosequencing, and the clinical parameters were analyzed. The associations between clinicopathological characteristics, including disease recurrence at follow-up (median 5.1 yr) and the percentage of mutant BRAF alleles were assessed. Results: The observed prevalence of BRAFV600E was higher when using pyrosequencing then when using BigDye Terminator sequencing (53.6 vs. 36.9%). In the PTC positive for BRAFV600E, the percentage of mutant alleles ranged from 5.1 to 44.7% of the total BRAF alleles, with a median of 20.6%. The presence or the percentage of BRAFV600E alleles did not correlate significantly with sex, multicentricity, lymph node metastasis, or tumor stage. The percentage of BRAFV600E alleles directly correlated with age at diagnosis and tumor volume (R2 = 0.223, P = 0.039, and R2 = 0.166, P <0.001, respectively). The percentage of BRAF V600E alleles (P = 0.014), tumor volume (P = 0.012), and lymph node metastasis (P = 0.008) predicted the disease outcome. The odds ratio of recurrence for PTC with BRAFV600E alleles of 30% or greater, compared with that for PTC with BRAFV600E alleles of less than 30%, was 5.31 (P = 0.002). Conclusions: A high percentage of BRAFV600E alleles defines a PTC molecular subtype and predicts a poorer disease outcome. The analysis of BRAF mutations by pyrosequencing is useful to refine the risk stratification of patients with PTC.
AB - Context: BRAFV600E is considered a negative prognostic marker in papillary thyroid carcinoma (PTC), but unexplained conflicting results are present in the literature. In light of the new finding that most PTC consist of a mixture of tumor cells with wild-type and mutant BRAF, we examined the associations between the percentage of BRAFV600E alleles and both the clinicopathological parameters at time of diagnosis and the disease outcome in a large series of PTCs. Study Design: Tumors from 168 patients with PTC were genotyped for BRAFV600E using BigDye Terminator sequencing and pyrosequencing, and the clinical parameters were analyzed. The associations between clinicopathological characteristics, including disease recurrence at follow-up (median 5.1 yr) and the percentage of mutant BRAF alleles were assessed. Results: The observed prevalence of BRAFV600E was higher when using pyrosequencing then when using BigDye Terminator sequencing (53.6 vs. 36.9%). In the PTC positive for BRAFV600E, the percentage of mutant alleles ranged from 5.1 to 44.7% of the total BRAF alleles, with a median of 20.6%. The presence or the percentage of BRAFV600E alleles did not correlate significantly with sex, multicentricity, lymph node metastasis, or tumor stage. The percentage of BRAFV600E alleles directly correlated with age at diagnosis and tumor volume (R2 = 0.223, P = 0.039, and R2 = 0.166, P <0.001, respectively). The percentage of BRAF V600E alleles (P = 0.014), tumor volume (P = 0.012), and lymph node metastasis (P = 0.008) predicted the disease outcome. The odds ratio of recurrence for PTC with BRAFV600E alleles of 30% or greater, compared with that for PTC with BRAFV600E alleles of less than 30%, was 5.31 (P = 0.002). Conclusions: A high percentage of BRAFV600E alleles defines a PTC molecular subtype and predicts a poorer disease outcome. The analysis of BRAF mutations by pyrosequencing is useful to refine the risk stratification of patients with PTC.
UR - http://www.scopus.com/inward/record.url?scp=84863574283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863574283&partnerID=8YFLogxK
U2 - 10.1210/jc.2011-3106
DO - 10.1210/jc.2011-3106
M3 - Article
C2 - 22508706
AN - SCOPUS:84863574283
VL - 97
SP - 2333
EP - 2340
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 7
ER -