On the contrary, no link could be detected between expression of BRAF(V599E) and age at diagnosis, gender, dimension, and local invasiveness of the primary cancer, presence of lymph node metastases, tumor stage, and multifocality of the disease.
In a series of 33 cases, 21 harbored the T1799A mutation in the primary tumors, and 17 (81%) of them harbored the same mutation also in the paired lymph node metastases.
While univariate analysis showed the BRAF(V600E) mutation was associated with tumour recurrence (21% with mutation vs 7% without mutation; P = 0.037), this association was not shown following multivariate analyses adjusting for the clinicopathological prognostic factors of age, gender, tumour size, extrathyroid extension, multifocality and lymph node metastasis.
Mutational patterns identical to those in the primary tumors were found in 11/12 lymph node metastases (92%, including both BRAF(T1799A)-positive and -negative cases).
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.
In this study, the BRAF (V600E) mutation in 54 PTCs was investigated and the relationship between the BRAF mutation and clinicopathological features such as age, gender, tumor size, extrathyroid extension, lymph node metastasis, and distant metastasis was analyzed.
We analyzed the expression of S100A4, cyclin D1, p27 and MUC1, the presence of the BRAF V600E mutation and the clinicopathological features of the tumors, including patient age, tumor size (>or=5 vs <5 mm), extrathyroidal extension, multifocality, histological subtype, sclerosis and encapsulation, in a series of 198 papillary microcarcinomas in relation to lymph node metastasis to determine the predictive factors of lymph node metastasis.
Hypermethylation of the DNA mismatch repair gene hMLH1 and its association with lymph node metastasis and T1799A BRAF mutation in patients with papillary thyroid cancer.
Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC.
In thyroid cancer, the V600E mutation occurs with greater frequently in aggressive subtypes of PTC, and in individuals that present at advanced stages of disease with extra-thyroidal extension and/or lymph node metastases.
On univariate analysis, the BRAF(V600E) mutation was associated with extrathyroidal extension (P = .009) and variants of PTC (P = .019), but a high-risk Metastasis, Patient Age, Completeness of resection, local Invasion and Tumor Size (MACIS) score (≥ 6) (P = .146) and lymph node metastasis (P = .628) were not significantly associated with the BRAF(V600E) mutation.
Moreover, BRAF(V600E) mutation was not correlated with any of the prognostic factors including age ≥45 years, male gender, tumor size ≥1cm, multifocality, extra-thyroidal extension, concurrent Hashimoto's thyroiditis, and lymph node metastasis neither in the univariate nor in the multivariate analysis.
In 26 studies, compared with the patients who had the wild-type BRAF genes, the PTC patients with the BRAF(V600E) mutation had increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68-2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21-1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61-2.49).
The BRAF(V600E) mutation was significantly associated with age (≥ 45 years), tumor size (>1 cm), extrathyroidal extension, and cervical lymph node metastases (P < 0.05).
Tumor size correlated significantly with multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.003, P < 0.001 and P < 0.001, respectively), but the BRAF V600E mutation status was not associated with any of those features.
Further, no significant correlation of V600E expression with clinicopathologic parameters of aggressiveness such as lymph node metastasis, peritumoral infiltration, or perithyroidal infiltration was found.
Additionally, there were significant associations (P<0.05) between BRAF(V600E) and a higher tumor-node-metastasis staging (III/IV), and between miR-21* over-expression and lymph node metastasis.