BRAF(V600E) mutation-positive cancers (55.3%) were more frequently associated with lymph node metastasis (p=0.01) and advanced TNM stage (III-IV) (p=0.03).
Considering all tumor foci, the all BRAF(V600E) mutation group exhibited a younger population (P = .039), showed increased extrathyroidal invasion (38.8% vs 14.7%, P = .017) and lymph node metastasis (71.4% vs 48.4%, P = .038), and received more radioactive iodine therapy (79.2% vs 52.9%, P = .012) than the mixed BRAF(V600E) mutation group.
The BRAF(V600E) mutation was associated with male sex (P = 0.028), large tumor size, extrathyroidal extension, central and lateral lymph node metastasis, and advanced tumor stage (P<0.0001).
The patients with BRAF p.Val600Glu mutation of primary tumour had only non-significantly higher risk of cervical lymph node metastases [OR=2.39 (95%) CI 1.00-5.75, p=0.052].
Multivariate analysis showed a strong association of MUC1 expression with the presence of the BRAF(V600E) mutation and lymph node metastasis (p<0.0001).
There was no statistically significant correlation in age, gender, multifocality, extrathyroidal extension, presence of Hashimoto thyroiditis, and lymph node metastasis between the BRAF(V600E) mutant group and wild group.
No significant differences were observed in either the occurrence or the allele percentage of V600E mutation between the 2 groups of PTCs with or without LNMs.
The presence of PB was significantly correlated with tumor multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.009, P = 0.004, and P < 0.001, respectively), but not with the BRAF(V600E) mutation.
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.
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.
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.
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).
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).
Further, no significant correlation of V600E expression with clinicopathologic parameters of aggressiveness such as lymph node metastasis, peritumoral infiltration, or perithyroidal infiltration was found.
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.
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.
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.