Univariant analysis indicated that capsular invasion, Hashimoto's thyroiditis, multifocal loci, central lymph node metastases as well as BRAF mutation predicted a high incidence of occult contralateral carcinoma.
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.
Usually, mutations in the codons 600 or 601 lead to constitutive activity in the Ras-mitogen-activated protein kinase pathway and, recently, the BRAF deletion was described as a relevant risk factor for loco-regional PTC lymph node metastasis.
We found significant association between BRAF (V600E) mutation and age (P < 0.0001), extrathyroidal invasion (P = 0.017), lymph node metastasis (P = 0.038) and TNM stage III/IV (P = 0.001).
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.
The absence of suspicious US features together with negative BRAF testing predicted PTC without extrathyroidal extension or lymph node metastasis (negative predictive value 88%).
The BRAF mutation was found to be an independent indicator of tumor bilaterality (odds ratio [OR] 1.484, P = .010); however, it was not an independent indicator of CLNM (OR 1.167, P = .254) or lateral lymph node metastasis (OR 0.647, P = .384).
Hypermethylation of the DNA mismatch repair gene hMLH1 and its association with lymph node metastasis and T1799ABRAF mutation in patients with papillary thyroid cancer.
Preoperative BRAF mutation testing of FNAB specimens provides a novel tool to preoperatively identify PTC patients at higher risk for extensive disease (extrathyroidal extension and lymph node metastases) and those who are more likely to manifest disease persistence/recurrence.
The BRAF mutation status or BRAFCt values were not associated with any of the clinical-pathologic prognostic factors.In conclusion, a higher number of suspicious US features classified by the TIRADS, but not the BRAF mutation, are associated with lateral lymph node metastasis in patients with PTC, and can aid in the preoperative identification of patients at increased risk of lateral lymph node metastasis.
In wild-type BRAF patients, the mean BRAF mRNA level was higher in cases with a tumor > 2 cm than those with a tumor ≤ 2.0 cm (189.4 vs. 163.8, p = 0.046), and was also higher in cases with lymph node metastasis than in those without lymph node metastasis (188.5 vs. 157.9, p = 0.040).
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).
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.
Tumors with subclonal BRAF mutations were significantly smaller compared to tumors with clonal mutation (0.82 ± 0.38 cm vs 1.37 ± 0.57 cm, P = .005) and were less likely to have lymph node metastasis (0% vs 32%, P = .03).
Association of BRAFV600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers.