Lymph Node Metastasis In Thyroid Cancer Research Articles

Enhancement on CT for preoperative diagnosis of metastatic lymph nodes in thyroid cancer: a comparison across experience levels.

To investigate the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong lymph node (LN) enhancement in differentiated thyroid cancer (DTC), comparing them with qualitative analysis by radiologists of varying experience. This study included 463 LNs from 399 patients with DTC. Three radiologists independently analyzed strong LN enhancement on CT. Qualitative analysis of strong enhancement was defined as LN cortex showing greater enhancement than adjacent muscles on the arterial phase. Quantitative analysis included the mean attenuation value (MAV) of LN on arterial phase (LNA) and venous phase (LNV), LNA normalized to the common carotid artery (NAVCCA), internal jugular vein (NAVIJV), and sternocleidomastoid muscle (NAVSCM), attenuation difference [AD; (LNA - MAVSCM)], and relative washout ratio [((LNA - LNV)/LNA) × 100]. The interobserver agreement and diagnostic performance of the quantitative and qualitative analyses were evaluated. Interobserver agreement was excellent for all quantitative CT parameters (ICC, 0.83-0.94) and substantial for qualitative assessment (κ = 0.61). All CT parameters except for LNV showed good diagnostic performance for metastatic LNs (AUC, 0.81-0.85). NAVCCA (0.85, 95% CI: 0.8-0.9) and AD (0.85, 95% CI: 0.81-0.89) had the highest AUCs. All quantitative parameters except for NAVIJV had significantly higher AUCs than qualitative assessments by inexperienced radiologists, with no significant difference from assessments by an experienced radiologist. Quantitative assessment of LN enhancement on arterial phase CT showed higher interobserver agreement and AUC values than qualitative analysis by inexperienced radiologists, supporting the need for a standardized quantitative CT parameter-based model for determining strong LN enhancement. When assessing strong LN enhancement in DTC, quantitative CT parameters indicating strong enhancement can improve interobserver agreement, regardless of experience level. Therefore, the development of a standardized diagnostic model based on quantitative CT parameters might be necessary. Accurate preoperative assessment of LN metastasis in thyroid cancer is crucial. Quantitative CT parameters indicating strong LN enhancement demonstrated excellent interobserver agreement and good diagnostic performance. Quantitative assessment of contrast enhancement offers a more objective model for the identification of metastatic LNs.

Diagnosing postoperative lymph node metastasis in thyroid cancer with multimodal radiomics and clinical features.

This study aims to evaluate the diagnostic value of texture analysis for lymph node metastasis after thyroid cancer surgery. We retrospectively analyzed patients who underwent positron emission tomography/computed tomography (PET/CT) examination before 131I treatment at Shanghai Tenth People's Hospital between 2017 and 2020. Clinical follow-up results were used as the criterion for determining the presence of lymph node metastasis. The study included 119 patients, who were then randomly divided into training and test groups in a 7:3 ratio. Regions of interest were identified, and radiomics features were extracted using LIFEx 7.3.0. Mann-Whitney U test and LASSO regression were employed to screen radiomics parameters for modeling. Subsequently, a nomogram model was built by combining radscore and clinical features. SPSS 26.0 software was utilized for statistical analysis, and p < 0.05 was considered statistically significant. Follow-up confirmed 54 patients with thyroid cancer lymph node metastasis and 65 patients in the non-metastasis group. A total of 119 lymph nodes were delineated. For each lesion, 164 CT texture features and 164 PET texture features were extracted, and 107 significant parameters were identified, including 16 CT texture parameters and 91 PET texture parameters. After screening, 3 CT parameters, 4 PET parameters and 12 PET/CT parameters were selected to establish three radiomic models. The AUC values were as follows: AUC (CT) = 0.730, AUC (PET) = 0.759 and AUC (PET/CT) = 0.864. We then combined clinical features and radscore to construct a nomogram, resulting in a C-index of 0.915 in the training group. In the test group, the C-index was confirmed to be 0.868. Radiomics may enhance the diagnostic efficiency of lymph node metastases after thyroid cancer surgery and could potentially assist clinicians in future diagnoses. The developed nomogram, which combines radiomics and clinical features, offers relatively high accuracy in helping clinicians assess the risk of metastasis in thyroid patients after surgery.

Quantification performance of silicon photomultiplier-based PET for small 18F-, 68Ga- and 124I-avid lesions in the context of radionuclide therapy planning

PurposeThe aim of this study was to investigate conditions for reliable quantification of sub-centimeter lesions with low18F,68Ga, and124I uptake using a silicon photomultiplier-based PET/CT system. MethodsA small tumor phantom was investigated under challenging but clinically realistic conditions resembling prostate and thyroid cancer lymph node metastases (6 spheres with 3.7–9.7 mm in diameter, 9 different activity concentrations ranging from about 0.25–25 kBq/mL, and a signal-to-background ratio of 20). Radionuclides with different positron branching ratios and prompt gamma coincidence contributions were investigated. Maximum-, contour-, and oversize-based partial volume effect (PVE) correction approaches were applied. Detection and quantification performance were estimated, considering a ±30 % deviation between imaged-derived and true activity concentrations as acceptable. A standard and a prolonged acquisition time and two image reconstruction algorithms (time-of-flight with/without point spread function modelling) were analyzed. Clinical data were evaluated to assess agreement of PVE-correction approaches indicating lesion quantification validity. ResultsThe smallest 3.7-mm sphere was not visible. If the lesions were clearly observed, quantification was, except for a few cases, acceptable using contour- or oversized-based PVE-corrections. Quantification accuracy did not substantially differ between 18F, 68Ga, and 124I. No systematic differences between the analyzed reconstruction algorithms or shorter and larger acquisition times were observed. In the clinical evaluation of 20 lesions, an excellent statistical agreement between oversize- and contour-based PVE-corrections was observed. ConclusionsAt the lower end of size (<10 mm) and activity concentration ranges of lymph-node metastases, quantification with reasonable accuracy is possible for 18F, 68Ga, and 124I, possibly allowing pre-therapeutic lesion dosimetry and individualized radionuclide therapy planning.

PTC-MAS: A Deep Learning-Based Preoperative Automatic Assessment of Lymph Node Metastasis in Primary Thyroid Cancer.

Identifying cervical lymph node metastasis (LNM) in primary thyroid cancer preoperatively using ultrasound is challenging. Therefore, a non-invasive method is needed to assess LNM accurately. To address this need, we developed the Primary Thyroid Cancer Lymph Node Metastasis Assessment System (PTC-MAS), a transfer learning-based and B-mode ultrasound images-based automatic assessment system for assessing LNM in primary thyroid cancer. The system has two parts: YOLO Thyroid Nodule Recognition System (YOLOS) for obtaining regions of interest (ROIs) of nodules, and LMM assessment system for building the LNM assessment system using transfer learning and majority voting with extracted ROIs as input. We retained the relative size features of nodules to improve the system's performance. We evaluated three transfer learning-based neural networks (DenseNet, ResNet, and GoogLeNet) and majority voting, which had the area under the curves (AUCs) of 0.802, 0.837, 0.823, and 0.858, respectively. Method III preserved relative size features and achieved higher AUCs than Method II, which fixed nodule size. YOLOS achieved high precision and sensitivity on a test set, indicating its potential for ROIs extraction. Our proposed PTC-MAS system effectively assesses primary thyroid cancer LNM based on preserving nodule relative size features. It has potential for guiding treatment modalities and avoiding inaccurate ultrasound results due to tracheal interference.

An integrated nomogram combining deep learning, clinical characteristics and ultrasound features for predicting central lymph node metastasis in papillary thyroid cancer: A multicenter study.

Central lymph node metastasis (CLNM) is a predictor of poor prognosis for papillary thyroid carcinoma (PTC) patients. The options for surgeon operation or follow-up depend on the state of CLNM while accurate prediction is a challenge for radiologists. The present study aimed to develop and validate an effective preoperative nomogram combining deep learning, clinical characteristics and ultrasound features for predicting CLNM. In this study, 3359 PTC patients who had undergone total thyroidectomy or thyroid lobectomy from two medical centers were enrolled. The patients were divided into three datasets for training, internal validation and external validation. We constructed an integrated nomogram combining deep learning, clinical characteristics and ultrasound features using multivariable logistic regression to predict CLNM in PTC patients. Multivariate analysis indicated that the AI model-predicted value, multiple, position, microcalcification, abutment/perimeter ratio and US-reported LN status were independent risk factors predicting CLNM. The area under the curve (AUC) for the nomogram to predict CLNM was 0.812 (95% CI, 0.794-0.830) in the training cohort, 0.809 (95% CI, 0.780-0.837) in the internal validation cohort and 0.829(95%CI, 0.785-0.872) in the external validation cohort. Based on the analysis of the decision curve, our integrated nomogram was superior to other models in terms of clinical predictive ability. Our proposed thyroid cancer lymph node metastasis nomogram shows favorable predictive value to assist surgeons in making appropriate surgical decisions in PTC treatment.

A prognostic nomogram for papillary thyroid cancer lymph node metastasis based on immune score.

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer and is characterized by an overall good prognosis and early-stage lymph node metastasis. The immune microenvironment is believed to play a crucial role in PTC initiation, progression and metastasis. However, to our knowledge, prognostic tools for thyroid cancer metastasis based on immune scores have not been adequately explored. This study aimed to construct a clinical nomogram to predict lymph node metastasis in patients with PTC. The genomic data and clinical-pathological characteristics of 447 PTC subjects were obtained from TCGA (The Cancer Genome Atlas data). Logistic regression models were performed for univariate and multivariate analyses to identify significant prediction factors. A prognostic nomogram was built based on the multivariate analysis results. The concordance index (C-index) and calibration curve were used to assess the predictive accuracy and discriminative ability of the model. The patients were divided into two subgroups based on immune scores. We found that patients with high immune scores had significantly higher lymph node metastasis risks (OR and 95% confidence interval [CI]: 1.774[1.130-2.784]) than those with low immune scores. The C-index for lymph node metastasis was 0.722 (95% CI, 0.671-0.774), which had a favorable performance for clinical prediction. The calibration curve for lymph node metastasis showed significant agreement between the nomogram prediction and actual observation. High immune scores are significantly correlated with higher lymph node metastasis risk in patients with PTC. Immune score-based prognostic nomograms may help to predict lymph node metastasis and have potential clinical application possibilities.

Diagnostic performance of ultrasound and computed tomography in parallel for the diagnosis of lymph node metastasis in patients with thyroid cancer: a systematic review and meta-analysis.

BackgroundCurrently, there is no evidence-based medical evidence for the diagnosis of lymph node metastasis (LNM) of thyroid cancer (TC) by ultrasound combined with computed tomography (US + CT), and the results of various studies on its diagnostic efficacy are inconsistent. Therefore, the diagnosis of cervical LNM by US + CT is controversial at present. The aims of the present systematic review and meta-analysis were to evaluate the diagnostic performance of US + CT in parallel for diagnosing cervical LNM in patients with TC.MethodsWe searched PubMed, EMBASE, Cochrane Library, Web of Science, and Wanfang Medical Network (Core journals only) for studies prior to May 2022 on the performance of US and CT in parallel for diagnosing cervical lymph nodes. The studies were screened according to inclusion and exclusion requirements, and the methodologic quality of the included studies was independently assessed by 2 reviewers using tailored questionnaires and criteria provided by Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We calculated the sensitivity, specificity, and diagnostic odds ratio (DOR) of cervical LNM for the central region, lateral neck, and whole neck. Meta-regression was performed to determine which parameters caused high diagnostic heterogeneity.ResultsWe included 11 studies of 6,261 patients with TC and 8,394 non-TC patients were included in the study. Most of the risk assessments included in the study were low risk, with no high-risk items. For the parallel test of US + CT, pooled sensitivity and specificity in the central region and lateral neck were 0.73 [95% confidence interval (CI): 0.56–0.85] and 0.80 (95% CI: 0.72–0.85), respectively. The calculated positive likelihood ratio was 3.6 (95% CI: 2.9–4.4), negative likelihood ratio was 0.34 (95% CI: 0.20–0.56), and DOR was 11 (95% CI: 6–18). The area under the curve was 0.83. For US + CT, the pooled sensitivity and specificity in the central region and lateral neck were 0.73 (95% CI: 0.56–0.85) and 0.80 (95% CI: 0.72–0.85), respectively.DiscussionThe diagnostic efficiency of CT for lateral cervical LNM is greater than for central cervical LNM. CT has high sensitivity and accuracy for the diagnosis of central cervical LNMs. US + CT is important for the preoperative examination of cervical LNMs in TC.

A case report of anaplastic thyroid cancer and papillary thyroid cancer lymph node metastasis: an unusual presentation as an invasive hypopharyngeal mass

Anaplastic thyroid carcinoma is a rare undifferentiated tumour of the thyroid follicular epithelium. It almost always develops from a pre-existing well-differentiated thyroid cancer with a co-existent thyroid malignancy varying from 5 to 17% . The co-existence of papillary thyroid cancer (PTC) with anaplastic thyroid cancer is a rare occurrence in metastases outside the primary thyroid lesion. Traditionally, this has been regarded as an aggressive form of cancer associated with a dismal prognosis. Recently, the focus has shifted to the development of novel therapies based on the availability of comprehensive genomic profiling platforms (CGP) with a rapid turn-around to identify molecular aberrations in tumours which acts as potential therapeutic targets. In the United Kingdom, we report the case of a 60-year-old woman with an unusual presentation of (metastatic) anaplastic thyroid carcinoma and concomitant papillary thyroid cancer metastasis within a contralateral lymph node. This was initially perceived as a left pyriform fossa mass involving and compressing her left hemi-larynx on clinical and radiological examination. Following the identification of BRAF V600E mutation on CGP, she was started on targeted therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib and demonstrated excellent clinical and radiological response following 7 months of treatment. She has subsequently undergone total thyroidectomy alongside with bilateral neck dissection, and is due to start radioactive iodine treatment to reduce the risk of recurrence of disease.

A Specific Predicting Model for Screening Skip Metastasis From Patients With Negative Central Lymph Nodes Metastasis in Papillary Thyroid Cancer.

Skip metastasis is a specific type of papillary thyroid cancer lymph node metastasis (LNM). The present study aimed to clarify the typical clinical characteristics of skip metastasis and optimize the prediction model, so as to provide a more individual treatment mode for skip metastasis. We retrospectively analyzed 1075 PTC patients with different lymph node metastasis statuses from two clinical centers. Comparisons have been made between patients with skip metastasis and other types of LNM. Univariate and multivariate analyses were performed to detect the risk factors for skip metastasis with negative LNM, and a nomogram for predicting skip metastasis was established. The rate of skip metastasis was 3.4% (37/1075). Compared with other types of LNM, significant differences showed in tumor size, upper portion location, thyroid capsular invasion, and ipsilateral nodular goiter with the central lymph node metastasis (CLNM) group, and in age and gender with the lateral lymph node metastasis (LLNM) group. Four variables were found to be significantly associated with skip metastasis and were used to construct the model: thyroid capsular invasion, multifocality, tumor size > 1 cm, and upper portion. The nomogram had good discrimination with a concordance index of 0.886 (95% confidence interval [CI], 0.823 to 0.948). In conclusion, the significant differences between skip metastasis and other types of LNM indicated that the lymph node drainage pathway of skip metastasis is different from either CLNM or LLNM. Furthermore, we established a nomogram for predicting risk of skip metastasis, which was able to effectively predict the potential risk of skip metastasis in patients without preoperative LNM clue.

Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma N-Glycomics.

BackgroundBiomarkers are needed for patient stratification between benign thyroid nodules (BTN) and thyroid cancer (TC) and identifying metastasis in TC. Though plasma N-glycome profiling has shown potential in the discovery of biomarkers and can provide new insight into the mechanisms involved, little is known about it in TC and BTN. Besides, several studies have indicated associations between abnormal glycosylation and TC. Here, we aimed to explore plasma protein N-glycome of a TC cohort with regard to their applicability to serve as biomarkers.MethodsPlasma protein N-glycomes of TC, BTN, and matched healthy controls (HC) were obtained using a robust quantitative strategy based on MALDI-TOF MS and included linkage-specific sialylation information.ResultsPlasma N-glycans were found to differ between BTN, TC, and HC in main glycosylation features, namely complexity, galactosylation, fucosylation, and sialylation. Four altered glycan traits, which were consecutively decreased in BTN and TC, and classification models based on them showed high potential as biomarkers for discrimination between BTN and TC (“moderately accurate” to “accurate”). Additionally, strong associations were found between plasma N-glycans and lymph node metastasis in TC, which added the accuracy of predicting metastasis before surgery to the existing method.ConclusionsWe comprehensively evaluated the plasma N-glycomic changes in patients with TC or BTN for the first time. We determined several N-glycan biomarkers, some of them have potential in the differential diagnosis of TC, and the others can help to stratify TC patients to low or high risk of lymph node metastasis. The findings enhanced the understanding of TC.

Value of Pyruvate Carboxylase in Thyroid Fine-Needle Aspiration Wash-Out Fluid for Predicting Papillary Thyroid Cancer Lymph Node Metastasis.

The incidence of papillary thyroid carcinoma (PTC) is increasing. Lymph node metastatic status of PTC is a major factor for decision marking of surgery and surgical extend, however, no reliable tool exists for prediction of PTC nodal metastasis, for example, ultrasound cannot qualitatively diagnose and effectively detect central lymph node metastasis (CLNM). Therefore, the development of a new diagnostic biomarker is crucial for CLNM. Metabolic dysregulation is an important factor associated with malignancy and metastasis of tumors. Pyruvate carboxylase (PC) is a major anaplerotic enzyme that catalyzes the carboxylation of pyruvate to form oxaloacetate, which has been suggested to be involved in the tumorigenesis of several cancers, including PTC. This study aimed to explore the role of PC expression in thyroid fine-needle aspiration (FNA) wash-out fluid for predicting CLNM in PTC, and to explore how PC is involved in PTC development. The expression levels of PC in PTC tissues and normal thyroid tissues were first compared based on bioinformatics analysis of public databases, including the Gene Expression Profiling (GEPIA), Oncomine and Gene Expression Omnibus (GEO) databases. Then, the PC mRNA and protein expression levels were measured by RT-PCR and Immunohistochemistry (IHC) in surgical tissues from a total of 42 patients with surgically confirmed PTC, and compared in patients with and without CLNM. Further, to assess PC expression in diagnostic biopsies, a total of 71 thyroid nodule patients with ultrasound-guided FNA wash-out fluid samples and cytological diagnosis were prospectively enrolled in the study. Then, we analyzed the mechanism of PC-mediated PTC progression in vitro. This study showed that PC expression was higher in PTC tissues and thyroid FNA wash-out fluid samples from patients with CLNM than those from patients without CLNM, and that PC-induced PTC metastasis may occur through the TGF-β/Smad-regulated epithelial–mesenchymal transition (EMT) pathway.

Lateral Neck Dissection for Papillary Thyroid Cancer.

Introduction: Lateral neck metastases occur in ~15% of papillary thyroid cancer and in ~40% of medullary thyroid cancer. We present herein a systematic approach to a standard comprehensive lateral neck dissection, with attention to specific areas where thyroid cancer lymph node metastases may be missed during surgery.Materials and Methods: Video demonstration of a comprehensive levels 2a, 3, 4, and 5b lateral neck dissection for thyroid cancer.Results: A systematic step-wise approach to a standard comprehensive lateral neck dissection for thyroid cancer, inclusive of levels 2a, 3, 4, and 5b, is demonstrated. Areas where thyroid cancer lateral neck lymph nodes can be missed are noted, including low level 4 nodes and carotid-vertebral nodes, level 5B nodes, and subdigastric level 2 nodes medial to the carotid artery.Conclusion: A step-wise systematic approach to a comprehensive lateral neck dissection for thyroid cancer may lower the risk for missed thyroid cancer lateral neck lymph node metastases.No competing financial interests exist.Runtime of video: 8 mins 35 secs

Diagnostic role of F-18 FDG PET/CT for preoperative lymph node staging in thyroid cancer patients; A systematic review and metaanalysis

PurposeAlthough ultrasonography (US) is a standard technique for the assessment of cervical lymph node (LN) metastasis, the role of F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is increasingly reported. The purpose of this study is to assess the diagnostic accuracy of F-18 FDG PET-CT for detection of cervical LN metastasis in thyroid cancer (TCa) patients through a meta-analysis. Patients and methodsThe PubMed, Cochrane Database, and Embase from the earliest available date of indexing through September 31, 2019, were searched for studies evaluating the diagnostic performance of F-18 FDG PET-CT for detection of LN metastasis in TCa. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. ResultsAcross 9 studies (759 patients), the pooled sensitivity for F-18 FDG PET-CT for all cervical LN metastasis in TCa was 0.30 (95% CI; 0.26–0.35) a pooled specificity of 0.94. For central LN metastasis, the pooled sensitivity was 0.28 (95% CI; 0.21–0.34) and a pooled specificity was 0.87 (95% CI; 0.83–0.90). For lateral LN metastasis, the pooled sensitivity was 0.56 (95% CI; 0.50–0.62) and a pooled specificity was 0.94. ConclusionsF-18 FDG PET-CT shows a low sensitivity and high specificity for the detection of metastatic LNs in patients with TCa. The current data suggests that F-18 FDG PET-CT is not indicated in the work up of patients with thyroid cancer or biochemical evidence of recurrent disease.

Integrated bioinformatics analysis to screen hub genes in the lymph node metastasis of thyroid cancer

Thyroid cancer (TC) is one of the most common types of malignancy of the endocrine-system. At present, there is a lack of effective methods to predict neck lymph node metastasis (LNM) in TC. The present study compared the expression profiles from The Cancer Genome Atlas between N1M0 and N0M0 subgroups in each T1-4 stages TC in order to identify the four groups of TC LNM-associated differentially expressed genes (DEGs). Subsequently, DEGs were combined to obtain a total of 493 integrated DEGs by using the method of Robust Rank Aggregation. Furthermore, the underlying mechanisms of LNM were investigated. The results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses demonstrated that the identified DEGs may promote LNM via numerous pathways, including extracellular matrix-receptor interaction, PI3K-AKT signaling pathway and focal adhesion. Following construction of a protein-protein interaction network, the significance score for each gene was calculated and seven hub genes were screened, including interleukin 6, actinin α2, collagen type I α 1 chain, actin α1, calbindin 2, thrombospondin 1 and parathyroid hormone. These genes were predicted to serve crucial roles in TC with LNM. The results from the present study could therefore improve the understanding of LNM in TC. In addition, the seven DEGs identified may be considered as potential novel targets for the development of biomarkers that could be used in the diagnosis and therapy of TC.

The Precursor for Nerve Growth Factor (proNGF) in Thyroid Cancer Lymph Node Metastases: Correlation with Primary Tumour and Pathological Variables.

Metastases in thyroid cancer are associated with aggressive disease and increased patient morbidity, but the factors driving metastatic progression are unclear. The precursor for nerve growth factor (proNGF) is increased in primary thyroid cancers, but its expression or significance in metastases is not known. In this study, we analysed the expression of proNGF in a retrospective cohort of thyroid cancer lymph node metastases (n = 56), linked with corresponding primary tumours, by automated immunohistochemistry and digital quantification. Potential associations of proNGF immunostaining with clinical and pathological parameters were investigated. ProNGF staining intensity (defined by the median h-score) was significantly higher in lymph node metastases (h-score 94, interquartile range (IQR) 50–147) than in corresponding primary tumours (57, IQR 42–84) (p = 0.002). There was a correlation between proNGF expression in primary tumours and corresponding metastases, where there was a 0.68 (95% CI 0 to 1.2) increase in metastatic tumour h-score for each unit increase in the primary tumour h-score. However, larger tumours (both primary and metastatic) had lower proNGF expression. In a multivariate model, proNGF expression in nodal metastases was negatively correlated with lateral neck disease and being male. In conclusion, ProNGF is expressed in locoregional metastases of thyroid cancer and is higher in lymph node metastases than in primary tumours, but is not associated with high-risk clinical features.

Fibronectin 1 promotes migration and invasion of papillary thyroid cancer and predicts papillary thyroid cancer lymph node metastasis.

Lymph node metastasis (LNM) is common in papillary thyroid cancer (PTC), and is an indicator of recurrence. The detailed molecular mechanism of LNM in PTC has not been well described. This study aimed to investigate the role of fibronectin 1 in PTC LNM and its clinical relevance. The expression of fibronectin 1 was confirmed in PTC tissues and cell lines. A correlation analysis was conducted and a receiver-operating characteristic curve obtained. The effect of fibronectin 1 on the proliferation of PTC cell lines was performed using a colony-formation assay and Cell Counting Kit 8. Cell-cycle analysis was performed with a flow-cytometry assay. Migration and invasion ability were evaluated by transwell and wound-healing assays. Fibronectin 1 was overexpressed in metastasized PTC. Overexpressed fibronectin 1 was positively correlated with PTC LNM. Receiver-operating characteristic analysis showed that the diagnostic accuracy of fibronectin 1 was 81.1%, with sensitivity of 80% and specificity of 82%. Overexpression of fibronectin 1 promoted proliferation, migration, and invasion in PTC. Fibronectin 1 plays a critical role in PTC metastasis by modulating the proliferation, migration, and invasion ability of PTC cells, and it is a valuable diagnostic biomarker for predicting PTC LNM.

Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.

A case of maxillary malignant ameloblastoma with cervical lymph node metastases of thyroid cancer

Statements of the Problem: We report a case of malignant ameloblastomawith cervical lymph nodemetastases of thyroid cancer. Materials and Methods: A 61-year-old male who had a swelling in his left maxillary and had visited a nearby dental clinic one month before, was referred to our hospital with the initial diagnosis of an ulcer in the left maxillary gingiva. Our preoperative diagnosis was maxillary malignant tumor. The patient had been suffering from mild diabetes and high blood pressure, and had been taking oral medicine to control these conditions. Method of Data Analysis: Two biopsy procedures revealed that the lesion was a malignant tumor. Though the histological type was not identified, adenosquamous cell carcinoma or odontogenic malignant tumor was suspected. We diagnosed it as a maxillary malignant tumor T4N1MO stage IVA. Preoperative selective intra-arterial chemotherapy and radiation therapy were conducted twice for the maxillary tumor. 40mg/body of docetaxel and 100mg/body of cisplatin were given through arteria femoralis respectively by means of the Seldinger method. Radiation therapy of 50Gy was also conducted.Diagnostic imaging showeda lymphnodemetastases in thecervical region. Since thehistological typewas not identified, cervical dissectionwas conducted.Cervical lymphnodemetastases of thyroid cancer was found in one of 32 submandibular lymph nodes. After conducting preoperative selective intra-arterial chemoradiotherapy, an operation was conducted to resect the malignant tumor in the maxillary under general anesthesia. Incision was conducted along the Weber’s incision line. The left maxillary bonewas resected completely while the inferior wall of the orbit was preserved, and split-thickness skin grafting was conducted. Pathological analysis revealed malignant ameloblastoma. A gastric fistula was made for nutritional care during the treatment. Results of Investigation: Although it was difficult to identify the histological type of the tumor by pathological analysis, squamous cell carcinoma, ameloblastoma carcinoma, adenoid cystic carcinoma or malignant ameloblastoma was suspected. Thyroid cancer (papillocarcinoma) was found in one of 32 accessory nerve lymph nodes through cervical dissection. Immunostaining showed a positive reaction to thyrogloblin andTTF-1. Reexamination of the biopsy lesion revealed that the tumorwas infiltrating and increasing in number, while forming alveolar configurations. Comedo-like necrotic focuses were observed in the inside of some alveolar configurations. The tumor cells

BTG1 expression in thyroid carcinoma: diagnostic indicator and prognostic marker.

We determined the expression and function of B cell translocation gene 1 (BTG1) in thyroid carcinoma. Thyroid samples were obtained from cancer lesions (n=83) and adjacent normal tissue (n=35) in thyroid cancer patients immediately after endoscopic biopsy. BTG1 expression was determined by immunohistochemistry and western blotting. The effect of BTG1 overexpression was examined invitro utilizing the human thyroid cancer cell line FTC-133, stably transfected with a recombinant lentivirus (LeBTG1 cells) and compared to empty vector transfected controls (LeEmpty). BTG1 overexpression was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. The expression of proteins involved in cell cycle regulation (cyclinD1), apoptosis (Bcl-2) and cell migration (MMP-9) in LeBTG1 cells was analyzed by western blotting. The effect of BTG1 overexpression on cell viability and proliferation was assessed by MTT assay in LeBTG1 and LeEmpty cells. Flow cytometric analyses were used to evaluate the effect of BTG1 expression on cell cycle distribution and apoptosis. The migration and invasion potential of LeBTG1 cells was examined by plating cells in Matrigel-coated chambers. BTG1 protein expression was significantly lower in thyroid cancer tissue biopsies compared to normal tissue as measured by immunohistochemistry (36.1 vs. 80.0% of tissues; P<0.05) and western blotting (0.251±0.021 vs. 0.651±0.065; P<0.05). Decreased expression of BTG1 was significantly correlated with thyroid cancer lymph node metastasis, clinical stage and pathological differentiation (P<0.05), as well as with reduced overall 10‑year survival rates compared to patients with higher expression levels (30.2 vs. 66.7%; P<0.05). Invitro analyses revealed that LeBTG1 cells had a reduced survival fraction compared to control LeEmpty cells, with higher rates of apoptosis (11.6±2.1 vs. 2.1±0.4%; P<0.05). The proportion of LeBTG1 cells in G0/G1 stage and S phase was also significantly different from LeEmpty cells (81.8±6.3 and 10.2±1.0%, vs. 62.4±4.9 and 25.5±2.6%, respectively; P<0.05), and the migration and invasion of LeBTG1 cells was significantly impaired with respect to LeEmpty cells (72.0±8.0 and 55.0±7.0 vs. 113.0±16.0 and 89.0±9.0, respectively; P<0.05). These effects were accompanied by decreased protein expression of cyclin D1, Bcl-2 and MMP-9 in LeBTG1 cells (0.234±0.018, 0.209±0.021, 0.155±0.017, respectively) compared to control LeEmpty cells (0.551±0.065, 0.452±0.043, 0.609±0.072, respectively; P<0.05). Reduced BTG1 expression is associated with increased disease severity, suggesting it is a negative regulator of thyroid cancer and can serve as a prognostic indicator.