Objective:To analyze the clinical significance of multigene assay in papillary thyroid carcinoma（PTC）. Methods:Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed. Results:Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients（P=0.023）. TERT promotor-mutated tumors had a large diameter（P=0.019）, a high proportion of multifocal lesions（P=0.050）, and a large number of lymph node metastases（P=0.031）. Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel（Cohen κ=0.694, 95%CI: 0.482-0.906, P<0.01）. In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age（P=0.029） and tumor size（P<0.01） among different pathological types. Conclusion:As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.
Humans ; Male ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/pathology* ; Proto-Oncogene Proteins B-raf/genetics* ; Clinical Relevance ; Carcinoma, Papillary/pathology* ; Mutation

Antiporters/genetics* ; Carcinoma, Papillary/pathology* ; Humans ; Neoplasm Metastasis/genetics* ; Sulfate Transporters/genetics* ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*

Objective: To investigate the effect of centrosomal protein Cep63 on the apoptosis of papillary thyroid carcinoma (PTC) cell lines TPC-1 and underlying mechanism. Methods: With collected PTC tissues and adjacent tissues, Cep63 expression was detected by RT-qPCR and its relationship with clinicopathological factors was analyzed. The experiment included negative control group (NC), low expression group (Cep63(-)) and overexpression group (Cep63(+)), and wild-type TPC-1 cells were transfected with Cep63 lentivirus. The efficiency of Cep63 was detected by western blot (WB) and qRT-PCR. Cell proliferation ability was detected by plate cloning experiment and MTT assay. Cell apoptotic rate was detected by flow cytometry, and expression levels of apoptosis-related proteins were detected by immunohistochemistry and WB. The t-test was used to compare the differences in the means between the two groups, the one-way analysis of variance was used to compare multiple groups, and the chi-square test was used to analyze the association between gene expression levels and pathological factors. Results: Compared with NC group, cell proliferation ability was significantly decreased in Cep63(-) group (3.18±0.07 vs. 2.14±0.09, t=8.54, P<0.01) and significantly increased in Cep63(+) group (3.18±0.07 vs. 3.58±0.10, t=3.21, P<0.05). Apoptotic rates in NC, Cep63 (-) and Cep63 (+) groups were respectively 3.03%±0.24%, 8.66%±0.44% and 1.17%±0.44%, and the flow cytometry showed that the low expression of Cep63 significantly increased the apoptosis TPC-1 cells (F=157.7, P<0.001). Bcl-2 protein expression levels of NC, Cep63 (-) and Cep63 (+) groups were respectively 1.07±0.03, 0.49±0.01 and 1.99±0.09, and BAX protein expression levels of three groups were respectively 0.64±0.02, 1.06±0.01 and 0.21±0.03. WB showed that the expression level of Bcl-2 decreased (F=183.2, P<0.001), while the expression level of BAX was significantly up-regulated (F=283.7, P<0.001). Conclusion: Cep63 may regulate the apoptotic process of TPC-1 cells through Bcl-2/BAX pathway and Cep63 may be a potential oncogene of PTC.
Apoptosis ; Carcinoma, Papillary/genetics* ; Cell Cycle Proteins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

Carcinoma, Papillary/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; RNA, Long Noncoding/genetics* ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

In recent years, with the improvement of the sensitivity of examination equipment and the change of people's living environment and diet, the rate of thyroid cancer has risen rapidly, which has increased nearly five folds in 10 years. The pathogenesis, clinical manifestation, biological behavior, treatment and prognosis of thyroid carcinoma of different pathological types are obviously different. Papillary thyroid carcinoma (PTC) can develop at any age, which accounts for about 90% of thyroid cancer. It progresses slowly and has favourable prognosis, but lymph node metastasis appears easily. Whether PTC is accompanied by lymph node metastasis has an important impact on its prognosis and outcome. The Raf murine sarcoma viral oncogene homolog B(BRAF)gene mutation plays a crucial role in PTC lymph node metastasis. Having an in-depth understanding of the specific role and mechanism of BRAF gene mutation in PTC is expected to provide new ideas for diagnosis and treatment of PTC.
Animals ; Carcinoma, Papillary/genetics* ; Humans ; Lymphatic Metastasis ; Mice ; Mutation ; Oncogenes ; Proto-Oncogene Proteins B-raf/genetics* ; Thyroid Cancer, Papillary/genetics* ; Thyroid Neoplasms/genetics*

Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.
Carcinoma ; genetics ; radiotherapy ; Carcinoma, Papillary ; Humans ; Iodine Radioisotopes ; therapeutic use ; Mutation ; Prognosis ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics ; radiotherapy

OBJECTIVETo investigate the correlation of microRNA-155 (miR-155) expression with clinicopathological features of patients with papillary thyroid carcinoma (PTC) and explore the value of miR-155 in prognostic assessment of PTC.

METHODSWe collected 86 pairs of fresh PTC and adjacent tissues to examine the expression of miR-155 using fluorescent quantitative PCR. miR-155 expressions in the tissues were analyzed in relation to the clinicopathological features of the patients.

RESULTSCompared with the paired adjacent tissues, 69.8% (60/86) of the PTC tissues showed up-regulated miR-155 expression by 2.63∓2.73 folds. Up-regulated miR-155 expressions were associated with a larger tumor size (1.66∓0.96 vs 1.19∓0.52 cm, P=0.021), a higher likeliness of extrathyroid invasion (56.7% vs 23.1%, P=0.004), a higher rate of lymph node metastasis (70% vs 46.2%, P=0.036), a more advanced TNM stage, and a higher rate of III-IV stage of the tumor (20% vs 0%, P=0.014). The expression level of miR-155 in PTC tissues was positively correlated with lymph node metastasis (r=0.531, P=0.001).

CONCLUSIONPTC patients with miR-155 over-expression tend to have a greater tumor size, a greater likeliness of extrathyroid involvement, a higher rate of cervical lymph node metastasis and a more advanced TNM stage. The high expression of miR-155 in the tumor may indicate a poor prognosis of PTC patients.

Carcinoma, Papillary ; genetics ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; MicroRNAs ; genetics ; Neck ; Prognosis ; Thyroid Neoplasms ; genetics ; Up-Regulation

Radioiodine ablation (RIA) therapy is one of the most important treatments for papillary thyroid carcinoma (PTC), but some patients who received (131)I have radioiodine-refractory disease caused by the decreased expression of the Na(+)/I(-) symporter (NIS). BRAF(V600E) mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF(V600E) mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF(V600E) mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance (A) values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF(V600E) mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases (β=-0.0195, P=0.085), but in the subgroup without hashimoto's thyroiditis (HT), BRAF(V600E) mutation could significantly inhibit the NIS expression (β=-0.0257, P=0.046). The results indicate that BRAF(V600E) mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.
Adult ; Carcinoma ; genetics ; metabolism ; Carcinoma, Papillary ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Proto-Oncogene Proteins B-raf ; genetics ; Symporters ; genetics ; metabolism ; Thyroid Neoplasms ; genetics ; metabolism

Recent studies have demonstrated that the BRAF(V600E) mutation is associated with aggressive clinicopathological features of papillary thyroid carcinoma (PTC). However, the BRAF mutation as a prognostic biomarker in papillary thyroid microcarcinoma (PTMC) is unclear. A systematic search of the electronic databases, including Medline, Scopus, CNKI and the Cochrane Library was performed up to July 1, 2014. Outcomes of interest included age, gender, concomitant hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall cell variant of PTMC (TCVPTMC), multifocality, extrathyroidal extension (ETE) and lymph node metastasis (LNM). A total of 19 studies published from 2008 to 2014 comprising 2253 patients fulfilled the inclusion criteria and were included in the meta-analysis, and 1143 (50.7%) of these patients were BRAF mutation positive. BRAF mutation was associated with larger tumor size (OR: 1.64; 95% CI: 1.16-2.32), multifocality (OR: 1.58; 95% CI: 1.25-2.00), ETE (OR: 2.59; 95% CI: 2.03-3.29), LNM (OR: 1.73; 95% CI: 1.14-2.62), advanced stage (OR: 2.03; 95% CI: 1.14-3.64) and TCVPTMC (OR: 5.07; 95% CI: 1.49-17.27; P=0.009). Additionally, the BRAF mutation was found to be not associated with age, gender, concomitant hashimoto thyroiditis or nodular goiter (P>0.05 for all). This meta-analysis revealed that in patients with PTMC, BRAF mutation is associated with tumor size, multifocality, ETE, LNM, advanced stage and TCVPTMC, and it may be used as a predictive factor for prognosis of PTMC.
Adult ; Aged ; Biomarkers, Tumor ; genetics ; Carcinoma, Papillary ; genetics ; pathology ; Female ; Genetic Association Studies ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Prognosis ; Proto-Oncogene Proteins B-raf ; genetics ; Thyroid Neoplasms ; genetics ; pathology

OBJECTIVETo investigate the association of concomitant BRAFV600E mutation with central lymph node metastases in papillary thyroid carcinoma (PTC).

METHODSThe clinicopathological data of 126 PTC patients who underwent surgical treatment within a period of 2 years were retrospectively analyzed. The BRAF V600E gene mutation was detected by quantitative fluorescence PCR.

RESULTSThe BRAF mutation rate was 69.0% (87/126). The univariate analysis showed that BRAF mutation status was significantly associated with central lymph node metastasis (P<0.05), while the gender, multiple lesions, tumor size, extra-thyroidal invasion, Hashimoto's thyroiditis and tumor stage were not significantly associated with the BRAF mutation (P>0.05 for all). The multivariate analysis showed that only central lymph node metastasis was significantly correlated with BRAF mutation (P<0.05). When the diameter of tumor was ≤10 mm, BRAF mutation was statistically not significantly correlated to central lymph node metastasis (P>0.05). When the diameter of tumor was >10 mm, the central lymph node metastasis rate was significantly higher in patients with positive BRAF mutation than that in patients with a negative BRAF mutation (P<0.05).

CONCLUSIONSThe presence of BRAF mutation is an independent predictive factor for central lymph node metastasis. When PTC is with preoperative positive BRAF mutation, the cervical dissection should be routinely performed. The larger the tumor diameter is, the more important is the central lymph node dissection. There should be re-evaluated the necessity of preventative central lymph node dissection when the tumor diameter was ≤5 mm in patients with negative BRAF mutation.

Carcinoma ; epidemiology ; genetics ; metabolism ; Carcinoma, Papillary ; Hashimoto Disease ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; diagnosis ; genetics ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins B-raf ; genetics ; Retrospective Studies ; Thyroid Neoplasms ; epidemiology ; genetics ; metabolism