Article

The Prevalence and Prognostic Value of BRAF Mutation in Thyroid Cancer

Department of Surgery, University of California, San Francisco, San Francisco, California 94143-1674, USA.
Annals of Surgery (Impact Factor: 8.33). 09/2007; 246(3):466-70; discussion 470-1. DOI: 10.1097/SLA.0b013e318148563d
Source: PubMed

ABSTRACT

To examine the prevalence of BRAF mutation among thyroid cancer histologic subtypes and determine the association of BRAF mutation with indicators of poor prognosis for papillary thyroid cancer and patient outcome.
The appropriate extent of surgical treatment, adjuvant therapy and follow-up monitoring for thyroid cancer remains controversial. Advances in the molecular biology of thyroid cancer have helped to identify candidate markers of disease aggressiveness. A commonly found genetic alternation is a point mutation in the BRAF oncogene (BRAF V600E), which is primarily found in papillary thyroid cancer and is associated with more aggressive disease.
BRAF V600E mutation status was determined in 347 tumor samples from 314 patients with thyroid cancer (245 with conventional papillary thyroid cancer, 73 with follicular thyroid cancer, and 29 with the follicular variant of papillary thyroid cancer). Univariate and multivariate analyses were performed to determine the association of BRAF V600E with clinicopathologic factors and patient outcome.
: The prevalence of BRAF V600E mutation was higher in conventional papillary thyroid cancer (51.0%) than in follicular variant of papillary thyroid cancer (24.1%) and follicular thyroid cancer (1.4%) (P < 0.0001). In patients with conventional papillary thyroid cancer, BRAF V600E mutation was associated with older age (P = 0.0381), lymph node metastasis (P = 0.0323), distant metastasis (P = 0.045), higher TNM stage (I and II vs. III and IV, P = 0.0389), and recurrent and persistent disease (P = 0.009) with a median follow-up time of 6.0 years. Multivariate analysis showed that BRAF V600E mutation [OR (95% CI) = 4.2 (1.2-14.6)] and lymph node metastasis [OR (95% CI) = 7.75 (2.1-28.5)] were independently associated with recurrent and persistent disease in patients with conventional papillary thyroid cancer.
BRAF V600E mutation is primarily present in conventional papillary thyroid cancer. It is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer. Testing for this mutation may be useful for selecting initial therapy and for follow-up monitoring.

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Available from: Ann Griffin, Apr 10, 2014
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    • "The majority of studies have demonstrated that the BRAF V600E mutation is common in PTC and that the frequency varies from 18 to 87%. Although certain studies have indicated that geographical and histological subtype classification factors may account for these differences, the reliability of the detection method must also be taken into consideration (7,15). In the present study, multiplex allele-specific PCR combined with DHPLC was used to detect the mutation. "
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    ABSTRACT: The aim of the present study was to investigate the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) and to determine the correlation between this mutation and indicators of poor prognosis and outcome in patients with PTC. The BRAF V600E mutation status was analyzed in 187 tumor samples using the multiplex allele-specific PCR method. Univariate and multivariate analyses were performed to investigate the association of the BRAF V600E mutation with clinical features and patient outcome. The sensitivity of the multiplex allele-specific PCR combined with denaturing high-performance liquid chromatography reached ~1%. The BRAF V600E mutation was observed in 63.6% (119/187) of tumor tissues, predominantly in PTC specimens, and no BRAF mutation was identified in other benign-type thyroid diseases. The univariate analysis indicated that the BRAF V600E mutation was associated with age, tumor stage and prognosis (P<0.05). In addition, the frequency of the BRAF V600E mutation was significantly different in the central (75.3%) and lateral neck (49.3%) lymph nodes of patients with lymph node metastasis. Multivariate logistic regression analysis showed that the BRAF V600E mutation (HR, 2.471; 95% CI, 1.149-5.312) and lymph node metastasis (HR, 3.003; 95% CI, 1.027-8.771) are independent factors that predict tumor prognosis. Thus, the BRAF V600E mutation is an independent risk factor that may be used to predict thyroid cancer persistence/recurrence.
    Full-text · Article · Feb 2014 · Oncology letters
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    • "Several studies have shown an association between the BRAFV600E mutation and prognostic factors in PTC. Kebebewet al. reported the BRAFV600E mutation was associated with older age (P = 0.0381) [6]. However, Kim et al.[4] and Lee et al. [12] revealed that age was not associated with the BRAFV600E mutation. "
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    ABSTRACT: The BRAFV600E mutation, which accounts for about 60--80% papillary thyroid carcinoma(PTC), has been identifiedas a prognostic marker for risk stratification of PTC patients. However, the BRAFV600E mutation as a prognostic marker in papillary thyroid microcarcinoma (PTMC) is unclear. We performed a retrospective review of 101 patients who underwent surgery for PTMC. We studied the prevalence of the BRAFV600E mutation. The associations between the BRAFV600E mutation and clinicopathologic characteristics were analyzed. The BRAFV600E mutation was observed in 72 patients (71.3%). There was no statistically significant correlation in age, gender, multifocality, extrathyroidal extension, presence of Hashimoto thyroiditis, and lymph node metastasis between the BRAFV600E mutant group and wild group. The BRAFV600E mutation is not significantly associated with prognostic factors in PTMC.
    Full-text · Article · Nov 2013 · World Journal of Surgical Oncology
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    • "The BRAFV600E mutation in PTC has been investigated at many institutions, but the relationship between the BRAFV600E mutation and the clinicopathological features of PTC remain controversial. Several studies have reported that the BRAFV600E mutation is associated with a poor prognosis when combined with the aggressive clinicopathological features of PTC [8,9], whereas other studies have failed to demonstrate a statistically significant association between the BRAFV600E mutation and aggressive clinicopathological features [7,10]. Therefore, the purpose of this study was to evaluate the prevalence of the BRAFV600E mutation in PTC and to analyse the association between the BRAFV600E mutation and the clinicopathological features of PTC at a single institution. "
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    ABSTRACT: Background: The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). In recent studies, the BRAFV600E mutation has been associated with poor clinicopathological characteristics, such as lymph node metastasis, extrathyroidal extension, and advanced stage. However, other studies have failed to establish an association between the BRAFV600E mutation and clinicopathological features. Therefore, we investigated the relationship between the BRAFV600E mutation and its clinicopathological factors at a single institution. Methods: A total of 327 consecutive patients with PTC were enrolled in this study and underwent thyroid surgery at Yeouido St. Mary's Hospital between February 2010 and December 2011.BRAFV600E mutation analysis was performed using polymerase chain reaction (PCR)-based amplification of DNA extracted from paraffin-embedded tumour specimens. Results: The BRAFV600E mutation was detected in the tumours of 241 (73.7%) patients. Lymph node metastasis, TNM stage, and multifocality were not significantly associated with the BRAFV600E mutation. However, larger tumour size, extrathyroidal extension, histologic type (classic type), and concurrent Hashimoto's thyroiditis were associated with the BRAFV600E mutation in the univariate analysis, although no clinicopathological features were associated with the BRAFV600E mutation in the multivariate analysis. Conclusion: There was no idependent prognostic factor associated with BRAFV600E mutation status in this study. The BRAFV600E mutation is unlikely to serve as a prognostic factor for PTC.
    Full-text · Article · May 2013 · World Journal of Surgical Oncology
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