Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland, with a relatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, it significantly decreases the survival of PTC patients. The molecular mechanisms of DM in PTC have not been systematically studied. We performed whole exome sequencing and GeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched white blood cell samples from 20 PTC with DM and 46 PTC without DM. We identified somatic mutations, gene fusions and copy number alterations and analyzed their relationships with DM of PTC. BRAF‐V600E was identified in 73% of PTC, followed by RET fusions (14%) in a mutually exclusive manner (P < 0.0001). We found that gene fusions (RET, ALK or NTRK1) (P < 0.01) and chromosome 22q loss (P < 0.01) were independently associated with DM in both univariate and multivariate analyses. A nomogram model consisting of chromosome 22q loss, gene fusions and three clinical variables was built for predicting DM in PTC (C‐index = 0.89). The plasma circulating tumor DNA (ctDNA) detection rate in PTC was only 38.9%; however, it was significantly associated with the metastatic status (P = 0.04), tumor size (P = 0.001) and invasiveness (P = 0.01). In conclusion, gene fusions and chromosome 22q loss were independently associated with DM in PTC and could serve as molecular biomarkers for predicting DM. The ctDNA detection rate was low in non–DM PTC but significantly higher in PTC with DM.
Capsular invasion is an independent risk factor of DLN metastasis and DLN metastasis could be used as a predictor of lateral node metastasis. The dissection of DLN in PTC patients is recommended and lateral lymph node should be evaluated for patients with DLN positive.
Objective: The aim of this study was to investigate the incidence and risk factors for lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC). Subjects and methods: 356 patients diagnosed with PTC who underwent total thyroidectomy and central lymph node dissection and lateral lymph node dissection between January 2005 and December 2011 were enrolled. The relation between LLNM and clinicopathological features such as gender, age, tumor size, tumor spread, psammoma bodies, tumor multifocality, extrathyroidal extension (ETE), unilateral or bilateral disease, tumor primary location and central lymph node metastases (CLNM) was analyzed. Results: The rate of LLNM was 75.0%. In the univariate analysis, it was significantly associated with age, tumor size, tumor spread, extrathyroidal extension, primary tumor location and central lymph node metastasis (p < 0.05). In contrast, in the multivariate analysis, it was significantly associated with primary tumor location, central lymph node metastasis (p < 0.05) and tumor size > 1.5 cm with p = 0.05 but was unrelated to the other factors. Conclusion: Patients with PTC, with the primary tumor located in the upper part of the lobe and positive central compartment lymph node metastasis with a tumor size > 1.5 cm diameter are more likely to have LLNM. Therefore, more meticulous evaluations including the lateral lymph nodes should be performed before surgery. Arch Endocrinol Metab. 2016;60(5):492-9
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