Multi-gene assay and clinical characteristics research in papillary thyroid carcinoma

Abstract

Background: To investigate the significance of multi-gene assay in papillary thyroid carcinoma (PTC) patients in clinical practice.

Methods: From April to December 2019, medical records of 68 patients with PTC after the initial surgery were retrospectively collected and analyzed in terms of the relations between gene mutations and clinicopathological characteristics.

Results: RET/PTC rearrangement was not detected in BRAF V600E mutation patients (P<0.001). Besides, compared with wild-type patients, BRAF V600E mutation was associated with significantly older age (P=0.001) and a higher rate of extrathyroid invasion (P=0.023). Significantly higher BRAF V600E mutation rates were found in clinical lymph node-negative (P=0.041) and non-metastatic lateral lymph nodes (P=0.027) patients as RET/PTC rearrangement was associated with younger age (P=0.001) and the increasing metastatic number of lymph nodes (P=0.020). Compared to other gene mutations, the multivariate analysis showed that larger tumor size [odds ratio (OR), 8.831; 95% CI: 1.971-35.578; P=0.004], the BRAF V600E mutation alone(OR, 10.567; 95% CI: 1.748-63.873; P=0.010) or in combination with one additional gene mutation (OR, 8.654; 95% CI: 1.453-68.603; P=0.041), and Hashimoto's thyroiditis (OR, 0.112; 95% CI: 0.025-0.499; P=0.004) were all independent predictors for the prevalence of ETE.

Conclusions: BRAF V600E mutation was associated with older age and the aggressiveness of PTC but was independent of lymph node metastasis (LNM). RET/PTC rearrangement suggested more LNM in young patients with PTC. BRAF V600E mutation combined with other gene mutations, namely, multi-gene mutations, could indicate a higher aggressiveness in PTC.

Keywords: Papillary thyroid carcinoma (PTC); gene mutation; multi-gene assay.

Figure 1

Distribution of gene mutations in papillary thyroid carcinoma. The omitted part represents that 35 patients with BRAF V600E mutation alone are not shown in the figure. The red part expresses that patient with the corresponded gene mutation. The blank part means no mutation. num., number; BRAF, B-Raf proto-oncogene, serine/threonine kinase; CHEK2, checkpoint kinase 2; MED12, mediator complex subunit 12; ATM, ATM serine/threonine kinase; TERT, telomerase reverse transcriptase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; GNAS, guanine nucleotide-binding protein, α-stimulating complex locus; SPOP, speckle-type POZ protein; TSHR, thyroid stimulating hormone receptor; PTEN, phosphatase and tensin homolog; AXIN1, axin 1; TP53, tumor protein p53; RAC1, ras-related C3 botulinum toxin substrate 1; MEN1, multiple endocrine neoplasia 1; CDKN2C, cyclin-dependent kinase inhibitor 2C; NTPK1, neurotrophic tyrosine kinase, receptor, type 1; RB1, retinoblastoma 1; PPARG, peroxisome proliferator-activated receptor gamma; RET, rearranged during transfection.