Factor In Papillary Thyroid Carcinoma Research Articles

BRAF V600E mutation in thyroid carcinoma: a large-scale study in Han Chinese population

BackgroundThe prevalence of genetic mutations in thyroid cancer varies significantly among different ethnic backgrounds. The present study aimed to investigate the clinical potential of BRAF V600E in a large group of homogenous Han Chinese patients.MethodsFrom 2018 to 2021, 6232 thyroid disease patients who underwent thyroidectomy at our hospital were enrolled. We measured the diagnostic value of BRAF and plotted ROC curves. Patients with full clinical-pathological data were selected and divided into the BRAF mutation and wild type groups. We conducted univariate and multivariate analyses to quantify the differences in potential predictive factors of papillary thyroid carcinoma (PTC) patients between the groups. Kaplan–Meier survival analysis was used to estimate overall recurrence and recurrence rate.ResultsThe prevalence of BRAF V600E mutation was 86.0% in PTCs. The sensitivity and specificity of BRAF mutation for diagnosing PTC from suspicious lesions were 85.5% and 100%, respectively. The sensitivity and specificity of BRAF analysis in the indeterminate cytology group were 72.5% and 100%, respectively. BRAF mutation showed an independent association with older age, negative HT, larger tumor size, extrathyroidal extension, and multifocality in PTCs. In micro-PTCs (tumor size ≤ 1), the mutation was also positively correlated with progressive phenotypes of extrathyroidal extension and multifocality. BRAF mutation was associated with poorer recurrence-free probability in Kaplan–Meier survival analysis.ConclusionsThis large single-center study reveals that BRAF V600E is highly prevalent in the Han Chinese population and demonstrates BRAF V600E mutation testing has high diagnostic accuracy and its strong association with the progress of aggressiveness in PTCs and a higher probability of recurrence. BRAF mutation can serve as an accurate marker for diagnosis and decision-making with great value.

Analysis of risk factors for papillary thyroid carcinoma and the association with thyroid function indicators.

This study aims to analyze the relationship between papillary thyroid carcinoma (PTC) and various factors. The study involved two groups-PTC patients and non-PTC controls. We utilized binary logistic regression and Least Absolute Shrinkage and Selection Operator (Lasso) regression for variable selection and risk factor analysis. Correlation analysis was performed using Spearman's rank correlation. The diagnostic value of thyroid stimulating hormone (TSH) levels for PTC was assessed using Receiver Operating Characteristic (ROC) curves. PTC patients exhibited higher body mass index (BMI) (23.71 vs. 22.66, p<0.05) and TSH levels (3.38 vs. 1.59, p<0.05). Urinary iodine concentration (UIC) was an independent predictor of PTC (OR=1.005, p<0.05). The optimal TSH threshold for PTC diagnosis was 2.4 mIU/L [The Area Under the Curve (AUC)=67.3%, specificity=71.4%, sensitivity=70.1%]. TSH levels positively correlated with BMI (r=0.593, p<0.05) and UIC (r=0.737, p<0.05). UIC may be an independent predictor of PTC, and TSH levels have some diagnostic value for identifying PTC.

Association of HOTAIR, MIR155HG, TERC, miR-155, -196a2, and -146a Genes Polymorphisms with Papillary Thyroid Cancer Susceptibility and Prognosis

Polymorphisms in long non-coding RNA and microRNA genes may play a significant role in the susceptibility and progression of papillary thyroid carcinoma (PTC). The current study investigates the polymorphisms HOTAIR rs920778, MIR155HG rs1893650, TERC rs10936599, miR-155 rs767649, miR-196a2 rs11614913 and miR-146a rs2910164 in 102 PTC patients and 106 age- and sex-matched controls of the Caucasian Serbian population, using real-time PCR. We observed differences in genotype distributions of the HOTAIR rs920778 (p = 0.016) and MIR155HG rs1893650 (p = 0.0002) polymorphisms between PTC patients and controls. HOTAIR rs920778 was associated with increased PTC susceptibility (adjusted OR = 1.497, p = 0.021), with the TT variant genotype increasing the risk compared to the CC genotype (OR = 2.466, p = 0.012) and C allele carriers (CC + CT) (OR = 1.585, p = 0.006). The HOTAIR rs920778 TT genotype was associated with lymph node metastasis (p = 0.022), tumor recurrence (p = 0.016), and progression-free survival (p = 0.010) compared to C allele carriers. Multivariate Cox regression revealed that ATA risk (HR = 14.210, p = 0.000004) and HOTAIR rs920778 (HR = 2.811, p = 0.010) emerged as independent prognostic factors in PTC. A novel polymorphism, MIR155HG rs1893650, was negatively correlated with susceptibility to PTC, with TC heterozygotes exerting a protective effect (OR = 0.268, p = 0.0001). These results suggest that the polymorphisms HOTAIR rs920778 and MIR155HG rs1893650 could be potential prognostic and risk biomarkers in papillary thyroid carcinomas.

Multifocality as an adverse histopathological factor in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is characterized by various clinical and pathomorphological features, such as metastases to the locoregional lymph nodes and radioiodine resistance. It could also be diagnosed as a microcarcinoma coexisting with other benign thyroid pathologies or as multifocal growth. Of these, multifocality in PTC is considered an unfavourable pathomorphological feature. However, the research findings are controversial. Objective — to investigate and evaluate the clinical and pathohistological features of multifocal PTC (mPTC) in comparison with unifocal (single nodule) PTC. Materials and methods. Among the patients who underwent operative treatment at the clinical bases of the Department of Surgery, Institute of Biology, and Medicine at Taras Shevchenko National University of Kyiv, 91 were diagnosed with PTC and were included in the study. Results. Out of the 91 patients, 31 (34%) had mPTC and 60 (66%) had PTC. Bilateral mPTC was diagnosed in 23 (74%) patients, which is in line with other studies. It is also worth mentioning, that 5 (16%) patients were diagnosed with multifocal growth only at the stage of histopathology section, without preoperative or intraoperative evidence of multifocality. A significantly higher frequency of locoregional metastasis was found in the mPTC group in 17 (55%) patients as compared to 18 (30%) patients with PTC (p=0.025). Lateral neck dissection was performed in 13 (42%) patients with mPTC, and in 13 (22%) patients with PTC (р=0.0525). Frozen section pathology was performed in 17 (24 patients with mPTC, and in 4 (10%) patients with PTC (р &gt;0,05). Conclusions. A higher frequency of locoregional metastasis and a higher propensity for performing a lateral neck dissection are both indicators of a higher biological aggressiveness of the carcinoma in PTC multifocal growth.

CircPI4KA Overexpression Enhances Carcinogenesis and Glycolysis Metabolism in Papillary Thyroid Carcinoma by Causing the miR-1287-5p-Mediated NRP2 Expression Elevation.

Circular RNAs (circRNAs) are implicated in regulating the pathogenesis of papillary thyroid carcinoma (PTC). Herein, we aimed to investigate how circRNA phosphatidylinositol 4-kinase IIIα (circPI4KA, hsa_circ_0062389) functioned as an oncogene in PTC. CircPI4KA, microRNA-1287-5p (miR-1287-5p) and Neuropilin-2 (NRP2) level detection were completed by reverse transcription-quantitative polymerase chain reaction assay. Cell proliferation was assessed through Cell Counting Kit-8 assay, colony formation assay, and EdU assay. Transwell assay was used for detecting migration and invasion abilities. Cell migration was also determined by wound healing assay. Cell apoptosis was assessed using flow cytometry assay. The protein examination was performed using western blot. Glycolysis was evaluated via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted for target analysis. The role of circPI4KA in vivo was explored and analyzed via tumor xenograft assay. CircPI4KA was significantly upregulated in PTC tissues and cells. Knockdown of circPI4KA suppressed proliferation, migration, invasion, glycolysis, and induced apoptosis of PTC cells. CircPI4KA interacted with miR-1287-5p in PTC cells. The antitumor function of circPI4KA downregulation was reversed by inhibition of miR-1287-5p. The miR-1287-5p directly targeted NRP2, and circPI4KA elevated the NRP2 expression by sponging miR-1287-5p. PTC progression was impeded by miR-1287-5p via targeting NRP2. Silencing circPI4KA inhibited tumor growth in vivo through the miR-1287-5p/NRP2 axis. The collective results revealed that circPI4KA induced the upregulation of NRP2 via sponging miR-1287-5p, thus acting as a carcinogenic factor in PTC.

Overexpression of activated focal adhesion kinase correlates with adverse clinicopathological factors of papillary thyroid carcinoma

Overexpression of activated focal adhesion kinase correlates with adverse clinicopathological factors of papillary thyroid carcinoma

Radioactive iodine therapy strategies for distinct types of differentiated thyroid cancer: a propensity score-matched analysis.

The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated. DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching. 105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC. RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.

Soluble DPP4 can act as a diagnostic biomarker in Hashimoto's thyroiditis with thyroid papillary carcinoma.

Hashimoto's thyroiditis (HT) is an independent risk factor for papillary thyroid carcinoma (PTC), but the underlying mechanism remains unknown. The incidence of PTC in patients with HT is significantly elevated, and the presence of both HT and PTC contributes to a higher rate of misdiagnosis. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the thyroid nodule gene chip dataset from GEO Datasets. Serum and clinical data from 191 patients with thyroid nodules at the affiliated hospital were collected for analysis. Experimental techniques, including real-time quantitative PCR, ELISA, immunohistochemistry (IHC), and enzyme activity detection, were used to measure the level of dipeptidyl peptidase 4 (DPP4) in thyroid nodule tissues and serum. Thyroid nodules in patients with HT and PTC exhibit high levels of DPP4, along with elevated concentrations of soluble DPP4 in the serum. These findings demonstrate the potential predictive value of soluble DPP4 for PTC diagnosis. The concentration and enzymatic activity of soluble DPP4 in serum can serve as diagnostic biomarkers for patients with HT-associated PTC.

Implications of isthmic location as a risk factor in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) located in the isthmus generally has been known to have more extrathyroidal extension (ETE), lymph node involvement, and multifocality. The purpose of this study was to determine the clinical significance of an isthmic location of PTC. The records of 160 patients who underwent a total thyroidectomy due to a single, dominant isthmic PTC were retrospectively reviewed. The characteristics of isthmic cancer were compared with those of unilateral-lobar cancer in a PTC cohort at Seoul St. Mary's hospital. After propensity score matching for age, sex, and tumor size, 160 isthmic PTCs and 800 unilateral-lobar PTCs were compared. The clinicopathologic characteristics were analyzed to evaluate the prognostic significance of an isthmic tumor location. The isthmic group was significantly older (49.6 vs. 46.8 years, P=0.007) and had a smaller mean tumor size (0.8±0.4 vs. 1.0±0.7 cm, P<0.001) than the unilateral-lobar group. After propensity score matching, tumor size categories, ETE, multifocality, nodal metastasis and proportion of patients with more than five metastatic lymph nodes were similar in both groups. However, N1b cases were more frequent in the unilateral-lobar group both before and after propensity score matching. In multivariate analysis, isthmic location was not correlated with gross ETE, multifocality, and higher-risk N1 disease. Younger age and more than five metastatic nodes increased the risk of PTC recurrence. However, isthmic tumor location was not significantly correlated with recurrence-free survival. Isthmic location is not an independent risk factor for aggressive clinicopathologic features and is not related to PTC recurrence.

Identifying and analyzing the key genes shared by papillary thyroid carcinoma and Hashimoto's thyroiditis using bioinformatics methods.

Hashimoto's thyroiditis (HT) is a chronic autoimmune disease that poses a risk factor for papillary thyroid carcinoma (PTC). The present study aimed to identify the key genes shared by HT and PTC for advancing the current understanding of their shared pathogenesis and molecular mechanisms. HT- and PTC-related datasets (GSE138198 and GSE33630, respectively) were retrieved from the Gene Expression Omnibus (GEO) database. Genes significantly related to the PTC phenotype were identified using weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) were identified between PTC and healthy samples from GSE33630, and between HT and normal samples from GSE138198. Subsequently, functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors and miRNAs regulating the common genes in PTC and HT were forecasted using the Harmonizome and miRWalk databases, respectively, and drugs targeting these genes were investigated using the Drug-Gene Interaction Database (DGIdb). The key genes in both GSE138198 and GSE33630 were further identified via Receiver Operating Characteristic (ROC) analysis. The expression of key genes was verified in external validation set and clinical samples using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). In total, 690 and 1945 DEGs were associated with PTC and HT, respectively; of these, 56 were shared and exhibited excellent predictive accuracy in the GSE138198 and GSE33630 cohorts. Notably, four genes, Alcohol Dehydrogenase 1B (ADH1B), Active BCR-related (ABR), alpha-1 antitrypsin (SERPINA1), and lysophosphatidic acid receptor 5 (LPAR5) were recognized as key genes shared by HT and PTC. Subsequently, EGR1 was identified as a common transcription factor regulating ABR, SERPINA1, and LPAR5 expression. These findings were confirmed using qRT-PCR and immunohistochemical analysis. Four (ADH1B, ABR, SERPINA1, and LPAR5) out of 56 common genes exhibited diagnostic potential in HT and PTC. Notably, this study, for the first time, defined the close relationship between ABR and HT/PTC progression. Overall, this study provides a basis for understanding the shared pathogenesis and underlying molecular mechanisms of HT and PTC, which might help improve patient diagnosis and prognosis.

Clinical significance and diagnostic value of QPCT, SCEL and TNFRSF12A in papillary thyroid cancer.

To identify specific novel genes that could be used as diagnostic and prognostic factors in papillary thyroid carcinoma (PTC). Screening of differential genes by RNA sequencing (RNA-Seq) in normal thyroid, Hashimoto's thyroiditis, PTC combined with Hashimoto's thyroiditis and PTC tissues. The genes QPCT, SCEL and TNFRSF12A were selected by qRT-PCR and immunohistochemical pre-experiments. The GEPIA2 database, qRT-PCR, and immunohistochemical studies were used to confirm the target genes QPCT, SCEL, and TNFRSF12A. ROC curves were used to assess the diagnostic usefulness of these 3 genes for PTC in more detail. Functional enrichment analysis showed that QPCT, SCEL and TNFRSF12A were enriched in the pathways for peptidyl-pyroglutamic acid biosynthesis, keratinocyte differentiation, WNT signaling, apoptosis. GEPIA2 database analysis revealed that QPCT, SCEL and TNFRSF12A were high in thyroid cancer, and TC patients with lower TNFRSF12A levels had short survival. QPCT, SCEL and TNFRSF12A were elevated in PTC and thyroid adenoma. The mRNA diagnostic values were as follows: for QPCT, AUROC =0.891, 95% CI, 0.835-0.947; for SCEL, AUROC =0.921, 95% CI, 0.869-0.974; for TNFRSF12A, AUROC =0.884, 95% CI, 0.809-0.958. Immunohistochemical results showed that QPCT, SCEL, and TNFRSF12A differed to varying degrees between subgroups of thyroid tissue. SCEL was associated with BRAF V600E mutation status and stratification of recurrence risk, while TNFRSF12A was associated with Cyclin D1. The protein diagnostic values were as follows: for QPCT, AUROC =0.752, 95% CI, 0.685-0.819; for SCEL, AUROC =0.715, 95% CI, 0.645-0.784; for TNFRSF12A, AUROC =0.660, 95% CI, 0.587-0.734. QPCT, SCEL and TNFRSF12A are expected to be diagnostic markers for PTC.

Multifokal Papiller Tiroid Karsinomlu Hastalarda Total Tiroidektominin Sonuçları ve Patolojik Özellikleri

Aim: The incidence of thyroid cancer has increased dramatically in recent decades. Multifocality is considered a poor prognostic factor for papillary thyroid carcinoma (PTC). Patients with multifocal PTC (MPTC) are at high risk for local recurrence, as well as lymphatic and distal metastases. This study examined the features and outcomes of MPTC. Material and Methods: This retrospective study was conducted on 300 patients with PTC. Patients were classified into a multifocal group and a unifocal group. The pathological features of the PTC and the patients’ outcomes were analyzed and compared. Results: The multifocal group included 146 patients (48.7%), while the unifocal group included 154 patients (51.3%). The occurrence of multifocality was higher in females than in males (Odds ratio, OR: 2.37, 95% confidence interval, CI: 1.20-4.67, p=0.015). Tumor size of &amp;gt;1 cm in the multifocal group was larger than in the unifocal group (2.5 and 2.2 cm, respectively, p=0.021). Moreover, in multifocal group higher moderate risk of recurrence was detected than in the unifocal group (OR: 1.63, 95% CI: 1.01-2.60, p=0.044). At follow-up after treatment, MPTC patients had higher lymph node metastasis (OR: 2.89, 95% CI: 1.23-6.80, p=0.014). In addition, significantly higher thyroglobulin plasma levels (p=0.026) and disease recurrence (OR: 2.41, 95% CI: 1.05-5.52, p=0.037) were found in the multifocal group compared to the unifocal group. Conclusion: Patients with MPTC had a higher risk of disease recurrence, and multifocality was concluded to be an independent prognostic factor for overall disease recurrence.

Golgi-apparatus genes related signature for predicting the progression-free interval of patients with papillary thyroid carcinoma

BackgroundWe aimed to build a novel model with golgi apparatus related genes (GaGs) signature and relevant clinical parameters for predicting progression-free interval (PFI) after surgery for papillary thyroid carcinoma (PTC).MethodsWe performed a bioinformatic analysis of integrated PTC datasets with the GaGs to identify differentially expressed GaGs (DE-GaGs). Then we generated PFI-related DE-GaGs and established a novel GaGs based signature. After that, we validated the signature on multiple external datasets and PTC cell lines. Further, we conducted uni- and multivariate analyses to identify independent prognostic characters. Finally, we established a signature and clinical parameters-based nomogram for predicting the PFI of PTC.ResultsWe identified 260 DE-GaGs related to PFI in PTC. The functional enrichment analysis showed that the DE-MTGs were associated with an essential oncogenic glycoprotein biosynthetic process. Consequently, we established and optimized a novel 11 gene signature that could distinguish patients with poorer prognoses and predicted PFI accurately. The novel signature had a C-index of 0.78, and the relevant nomogram had a C-index of 0.79. Also, it was closely related to the pivotal clinical characters of and anaplastic potential in datasets and PTC cell lines. And the signature was confirmed a significant independent prognostic factor in PTC. Finally, we built a nomogram by including the signature and relevant clinical factors. Validation analysis showed that the nomogram’s efficacy was satisfying in predicting PTC’s PFI.ConclusionThe GaGs signature and nomogram were closely associated with PTC prognosis and may help clinicians improve the individualized prediction of PFI, especially for high-risk patients after surgery.

Relationship between serum NDRG3 and papillary thyroid carcinoma.

In recent years, papillary thyroid carcinoma is considered to be one of the fastest increaseing cancer. NDRG family member 3 (NDRG3) has been proposed as a molecular marker of tumor, and is expected to be used in clinic. Enzyme-linked immunosorbent assay was used to detect the serum NDRG3 expression in 81 papillary thyroid carcinoma cases, 75 benign thyroid nodules cases and 77 healthy control cases, respectively. Electrochemiluminescence method was applied to measure the levels of triiodothyronine, tetraiodothyronine, thyrotropin, thyroglobulin antibody and thyroid peroxidase antibody. Immunohistochemical staining was used to detect the expression of NDRG3 in papillary thyroid carcinoma, benign thyroid nodules and normal tissues adjacent to cancer. The expression of serum triiodothyronine, tetraiodothyronine, thyrotropin, thyroglobulin antibody and thyroid peroxidase antibody and NDRG3 were significantly different among benign thyroid nodules, papillary thyroid carcinoma cases and healthy control groups (P <0.001). Only the expression of serum NDRG3 was significantly different between benign thyroid nodules and papillary thyroid carcinoma groups (P <0.001). Immunohistochemistry showed that NDRG3 was expressed in all three groups, the lowest in papillary thyroid carcinoma, the second in benign thyroid nodules, and the highest in normal tissues adjacent to cancer. Logistic regression analysis showed that serum NDRG3 was an independent protective factor for papillary thyroid carcinoma (OR =0.964, 95%CI =0.953 to 0.974, P <0.001). The ROC curve of non-papillary thyroid carcinoma diagnosed by serum NDRG3 showed the optimal cut-off value of 481.38 pg/ml, sensitivity of 72.4%, specificity of 90.1%, and the maximum area under the curve (AUC =0.902, 95%CI =0.863 to 0.940, P <0.001). The ROC curve of benign thyroid nodules diagnosed by serum NDRG3 showed the optimal critical value of 459.28 pg/ml, sensitivity of 81.3%, and specificity of 74.1% (AUC =0.863, 95%CI =0.808 to 0.919, P <0.001). The expression level of serum NDRG3 was significantly correlated with extrathyroid extensionand (P =0.007) and lymphatic metastasis of papillary thyroid carcinoma (P =0.019). The decrease of NDRG3 expression can not only differential diagnosis benign thyroid nodules and papillary thyroid carcinoma, but also serve as a molecular marker for the diagnosis of papillary thyroid carcinoma.

Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study

IntroductionNon-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC.Materials and methodsPTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients.ResultsPathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91–8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60–8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs.ConclusionThe prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.

Evolution of intra-tumoral heterogeneity across different pathological stages in papillary thyroid carcinoma

BackgroundIntra-tumor heterogeneity (ITH) results from the continuous accumulation of mutations during disease progression, thus impacting patients’ clinical outcome. How the ITH evolves across papillary thyroid carcinoma (PTC) different tumor stages is lacking.MethodsWe used the whole-exome sequencing data from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort to track the ITH and assessed its relationship with clinical features through different stages of the PTC progression. We further assayed the expression levels of the specific genes in papillary thyroid cancer cell lines compared to an immortalized normal thyroid epithelial cell line by qRT-PCR.ResultsWe revealed the timing of mutational processes and the dynamics of the temporal acquisition of somatic events during the lifetime of the PTC. ITH significantly influences the PTC patient’s survival rate and, as genetic heterogeneity increases, the prognosis gets worse in advanced tumor stages. ITH also affects the mutational architecture of each clinical stage which is subject to periodic fluctuations. Different mutational processes may cooperate to shape a stage-specific mutational spectrum during the progression from early to advanced tumor stages. Moreover, different evolutionary paths characterize PTC progression across pathological stages due to both mutations recurrently occurring in all stages in hotspot positions and distinct codon changes dominating in different stages. A different expression level of specific genes also exists in different thyroid cancer cell lines.ConclusionsOur findings suggest ITH as a potential unfavorable prognostic factor in PTC and highlight the dynamic changes in different clinical stages of PTC, providing some clues for the precision medicine and suggesting different diagnostic decisions depending on the clinical stages of patients. Finally, complete clear guidelines to define risk stratification of PTC patients are lacking; thus, this work could contribute to defining patients who need more aggressive treatments and, in turn, could reduce the social burden of this cancer.

Ultrasound-based radiomics nomogram combined with clinical features for the prediction of central lymph node metastasis in papillary thyroid carcinoma patients with Hashimoto's thyroiditis.

BackgroundHashimoto thyroiditis (HT) is the most common autoimmune thyroid disease and is considered an independent risk factor for papillary thyroid carcinoma (PTC), with a higher incidence of PTC in patients with HT.ObjectiveTo build an integrated nomogram using clinical information and ultrasound-based radiomics features in patients with papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT) to predict central lymph node metastasis (CLNM).MethodsIn total, 235 patients with PTC with HT were enrolled in this study, including 101 with CLNM and 134 without CLNM. They were divided randomly into training and validation datasets with a 7:3 ratio for developing and evaluating clinical features plus conventional ultrasound features (Clin-CUS) model and clinical features plus radiomics scores (Clin-RS) model, respectively. In the Clin-RS model, the Pyradiomics package (V1.3.0) was used to extract radiomics variables, and LASSO regression was used to select features and construct radiomics scores (RS). The Clin-CUS and Clin-RS nomogram models were built using logistic regression analysis.ResultsTwenty-seven CLNM-associated radiomics features were selected using univariate analysis and LASSO regression from 1488 radiomics features and were calculated to construct the RS. The integrated model (Clin-RS) had better diagnostic performance than the Clin-CUS model for differentiating CLNM in the training dataset (AUC: 0.845 vs. 0.778) and the validation dataset (AUC: 0.808 vs. 0.751), respectively.ConclusionOur findings suggest that applying an ultrasound-based radiomics approach can effectively predict CLNM in patients with PTC with HT. By incorporating clinical information and RS, the Clin-RS model can achieve a high diagnostic performance in diagnosing CLNM in patients with PTC with HT.

Minimal extrathyroidal extension is associated with lymph node metastasis in single papillary thyroid microcarcinoma: a retrospective analysis of 814 patients

BackgroundExtrathyroidal extension (ETE) is considered a major prognostic factor in papillary thyroid carcinoma (PTC). Patients with gross ETE are at increased risk of recurrence and mortality. The importance of minimal ETE still remains controversial, especially in patients with papillary thyroid microcarcinoma (PTMC). The purpose of this study was to evaluate the association between ETE and lymph node (LN) metastasis in single PTMC.MethodsA retrospective analysis was performed of 1994 patients underwent thyroidectomy for PTC between 2012 and 2016 in a single institution. Patients with combined thyroid carcinoma of other types and those who underwent completion thyroidectomy were excluded. After further exclusion of PTC larger than 1 cm and multifocal tumors, 814 patients with single PTMC were included in the study.Results72.9% patients had no ETE, 25.1% minimal ETE, and 2.1% gross ETE. ETE was associated with lymphatic invasion, perineural invasion, and vascular invasion. Patients with minimal and gross ETE were also more likely to have LN metastasis, including lateral neck metastasis, compared to those without ETE. In univariate analysis, LN metastasis was associated with male gender, conventional PTC, lymphatic invasion, perineural invasion, and ETE. In multivariate analysis, male gender (OR = 1.987; 95% CI 1.369–2.884), lymphatic invasion (OR = 4.389; 95% CI 1.522–12.658), perineural invasion (OR = 6.545; 95% CI 1.262–33.948), and minimal ETE (OR = 1.852; 95% CI 1.298–2.643) were found to be independent risk factors of LN metastasis.ConclusionsMinimal ETE is associated with LN metastasis in single PTMC, compared to no ETE. Minimal ETE should be considered in the management of patients with single PTMC, whether surgical or during active surveillance.

Papillary Thyroid Carcinoma: Current Position in Epidemiology, Genomics, and Classification.

Papillary thyroid carcinoma is the most common type of thyroid malignancy both in adults and pediatric population. Since the 1980s, there are changes in criteria in labelling thyroid lesions as "papillary thyroid carcinomas." Radiation exposure is a well-established risk factor for papillary thyroid carcinoma. Other environmental risk factors include dietary iodine, obesity, hormones, and environmental pollutants. Papillary thyroid carcinomas could occur in familial settings, and 5% of these familial cases have well-studied driver germline mutations. In sporadic papillary thyroid carcinoma, BRAF mutation is common and is associated with clinicopathologic and prognostic markers. The mutation could aid in the clinical diagnosis of papillary thyroid carcinoma. Globally, thyroid cancer is among the top ten commonest cancer in females. In both adult and pediatric populations, there are variations of prevalence of thyroid cancer and rising incidence rates of thyroid cancer worldwide. The increase of thyroid cancer incidence was almost entirely due to the increase of papillary thyroid carcinoma. The reasons behind the increase are complex, multifactorial, and incompletely understood. The most obvious reasons are increased use of diagnostic entities, change in classification of thyroid neoplasms, as well as factors such as obesity, environmental risk factors, and radiation. The prognosis of the patients with papillary thyroid carcinoma is generally good after treatment. Nevertheless, cancer recurrence and comorbidity of second primary cancer may occur, and it is important to have awareness of the clinical, pathological, and molecular parameters of papillary thyroid carcinoma.

Expression of CXCR4 and CXCR7 in papillary thyroid carcinoma and adjacent tissues and their relationship with pathologic indicators of tumor aggressiveness

The receptors of chemokines play a significance role in the aggressiveness of tumor. CXCR4/CXCR7 promote metastasis of papillary thyroid carcinoma (PTC). This study examined the expresssion of chemokine receptors CXCR4/CXCR7 in human tissue specimens of PTC and peritumoral nonmalignant tissues. The correlation between CXCR4/CXCR7 and the clinicopathological factors in PTC was also determined. CXCR4/CXCR7 were examined in 115 PTC tissues from 115 patients using immunohistochemistry. Staining intensity was compared with patients and tumor characteristics including gender, age, tumor size, capsule invasion, multifocality, lymph node metastasis, and nature of paracancerous tissue. [Statistics: rank sum test, Spearman rank order correlation test; p < 0.05]. Higher expression rates of CXCR4/CXCR7 exhibited in PTC compared with peritumoral nonmalignant tissues. The expression of them was correlated in cancer and paracancerous specimens. A trend toward higher CXCR4/CXCR7 expression was found among tumors showing positive lymph nodes and capsule invasion, while no association with sex, age, tumor size, and nature of paracancerous tissue. Number of lymph nodes was associated with higher intensity IHC staining for CXCR4/CXCR7. Intense staining for CXCR4 was also associated with multifocality. Expression of CXCR4/CXCR7 by PTCs was correlated with lymph node metastasis and capsule invasion. Although multiple bias, they were thought to play a significance role in the aggressiveness of PTC, which provides potential targets for therapeutic interventions.