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Original Articles
Utilizing Immunoglobulin IgG4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis
Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung
Received January 2, 2024  Accepted February 28, 2024  Published online May 20, 2024  
DOI: https://doi.org/10.3803/EnM.2024.1923    [Epub ahead of print]
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AbstractAbstract PDFPubReader   ePub   
Background
Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished.
Methods
This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery.
Results
Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT.
Conclusion
This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.
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Thyroid
Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
Jinsun Lim, Han Sai Lee, Jin-Hyung Heo, Young Shin Song
Endocrinol Metab. 2024;39(2):324-333.   Published online April 4, 2024
DOI: https://doi.org/10.3803/EnM.2023.1885
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development.
Methods
We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining.
Results
Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group.
Conclusion
Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.
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Review Article
Thyroid
Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines
Min Joo Kim, Jae Hoon Moon, Eun Kyung Lee, Young Shin Song, Kyong Yeun Jung, Ji Ye Lee, Ji-hoon Kim, Kyungsik Kim, Sue K. Park, Young Joo Park
Endocrinol Metab. 2024;39(1):47-60.   Published online February 15, 2024
DOI: https://doi.org/10.3803/EnM.2024.1937
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AbstractAbstract PDFPubReader   ePub   
The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Citations

Citations to this article as recorded by  
  • 2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules
    Eun Kyung Lee, Young Joo Park
    Clinical Thyroidology®.2024; 36(4): 153.     CrossRef
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Original Articles
Thyroid
Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review
Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
Endocrinol Metab. 2024;39(1):152-163.   Published online January 22, 2024
DOI: https://doi.org/10.3803/EnM.2023.1794
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).
Methods
Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.
Results
In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%–10.8% and 16.0%–25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%–1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.
Conclusion
AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

Citations

Citations to this article as recorded by  
  • It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
    Kyeong Jin Kim
    Endocrinology and Metabolism.2024; 39(1): 95.     CrossRef
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Thyroid
Comparative Analysis of Driver Mutations and Transcriptomes in Papillary Thyroid Cancer by Region of Residence in South Korea
Jandee Lee, Seonhyang Jeong, Hwa Young Lee, Sunmi Park, Meesson Jeong, Young Suk Jo
Endocrinol Metab. 2023;38(6):720-729.   Published online November 6, 2023
DOI: https://doi.org/10.3803/EnM.2023.1758
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants.
Methods
We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared.
Results
No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAFV600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence.
Conclusion
Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients’ region of residence in South Korea.
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Thyroid
Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma
Jinsun Lim, Han Sai Lee, Jiyun Park, Kyung-Soo Kim, Soo-Kyung Kim, Yong-Wook Cho, Young Shin Song
Endocrinol Metab. 2023;38(4):445-454.   Published online July 18, 2023
DOI: https://doi.org/10.3803/EnM.2023.1702
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs.
Methods
We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment.
Results
Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status.
Conclusion
The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.

Citations

Citations to this article as recorded by  
  • Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways
    Dumitru Andrei Iacobas, Sanda Iacobas
    Genes.2024; 15(5): 621.     CrossRef
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Thyroid
Diagnostic Performance of Thyroid Core Needle Biopsy Using the Revised Reporting System: Comparison with Fine Needle Aspiration Cytology
Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, So Lyung Jung, Chan Kwon Jung
Endocrinol Metab. 2022;37(1):159-169.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2021.1299
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  • 7 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aim to validate the diagnostic performance of thyroid core needle biopsy (CNB) for diagnosing malignancy in clinical settings to align with the changes made in recently updated thyroid CNB guidelines.
Methods
We retrospectively analyzed 1,381 thyroid CNB and 2,223 fine needle aspiration (FNA) samples. The FNA and CNB slides were interpreted according to the Bethesda System for Reporting Thyroid Cytopathology and updated practice guidelines for thyroid CNB, respectively.
Results
Compared to FNA, CNB showed lower rates of inconclusive results: categories I (2.8% vs. 11.2%) and III (1.2% vs. 6.2%), and higher rates of categories II (60.9% vs. 50.4%) and IV (17.5% vs. 2.0%). The upper and lower bounds of the risk of malignancy (ROM) for category IV of CNB were 43.2% and 26.6%, respectively. The CNB subcategory IVb with nuclear atypia had a higher ROM than the subcategory without nuclear atypia (40%–62% vs. 23%–36%). In histologically confirmed cases, there was no significant difference in the diagnostic performance between CNB and FNA for malignancy. However, neoplastic diseases were more frequently detected by CNB than by FNA (88.8% vs. 77.6%, P=0.046). In category IV, there was no difference in unnecessary surgery rate between CNB and FNA (4.7% vs. 6.9%, P=0.6361).
Conclusion
Thyroid CNB decreased the rate of inconclusive results and showed a higher category IV diagnostic rate than FNA. The revised guidelines for thyroid CNB proved to be an excellent reporting system for assessing thyroid nodules.

Citations

Citations to this article as recorded by  
  • Examining the impact of several factors including COVID‐19 on thyroid fine‐needle aspiration biopsy
    Muzaffer Serdar Deniz, Merve Dindar
    Diagnostic Cytopathology.2024; 52(1): 42.     CrossRef
  • A comparative analysis of core needle biopsy and repeat fine needle aspiration in patients with inconclusive initial cytology of thyroid nodules
    Xuejiao Su, Can Yue, Wanting Yang, Buyun Ma
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy
    Hye Hyeon Moon, Sae Rom Chung, Young Jun Choi, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Jeong Hyun Lee, Jung Hwan Baek
    Endocrinology and Metabolism.2024; 39(2): 300.     CrossRef
  • Preoperative Risk Stratification of Follicular-patterned Thyroid Lesions on Core Needle Biopsy by Histologic Subtyping and RAS Variant-specific Immunohistochemistry
    Meejeong Kim, Sora Jeon, Chan Kwon Jung
    Endocrine Pathology.2023; 34(2): 247.     CrossRef
  • 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules
    Young Joo Park, Eun Kyung Lee, Young Shin Song, Soo Hwan Kang, Bon Seok Koo, Sun Wook Kim, Dong Gyu Na, Seung-Kuk Baek, So Won Oh, Min Kyoung Lee, Sang-Woo Lee, Young Ah Lee, Yong Sang Lee, Ji Ye Lee, Dong-Jun Lim, Leehi Joo, Yuh-Seog Jung, Chan Kwon Jung
    International Journal of Thyroidology.2023; 16(1): 1.     CrossRef
  • Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy
    Chan Kwon Jung
    Journal of Pathology and Translational Medicine.2023; 57(4): 208.     CrossRef
  • Consensus SFE-AFCE-SFMN 2022 sur la prise en charge des nodules thyroïdiens : intérêt et place de la cytologie thyroïdienne
    Myriam Decaussin-Petrucci, Beatrix Cochand Priollet, Emannuelle Leteurtre, Frédérique Albarel, Françoise Borson-Chazot
    Annales de Pathologie.2023;[Epub]     CrossRef
  • A Matched-Pair Analysis of Nuclear Morphologic Features Between Core Needle Biopsy and Surgical Specimen in Thyroid Tumors Using a Deep Learning Model
    Faridul Haq, Andrey Bychkov, Chan Kwon Jung
    Endocrine Pathology.2022; 33(4): 472.     CrossRef
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Thyroid
Clinicopathological Characteristics and Disease-Free Survival in Patients with Hürthle Cell Carcinoma: A Multicenter Cohort Study in South Korea
Meihua Jin, Eun Sook Kim, Bo Hyun Kim, Hee Kyung Kim, Yea Eun Kang, Min Ji Jeon, Tae Yong Kim, Ho-Cheol Kang, Won Bae Kim, Young Kee Shong, Mijin Kim, Won Gu Kim
Endocrinol Metab. 2021;36(5):1078-1085.   Published online October 28, 2021
DOI: https://doi.org/10.3803/EnM.2021.1151
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.
Methods
This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.
Results
The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).
Conclusion
The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.

Citations

Citations to this article as recorded by  
  • Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma
    Lindsay A. Bischoff, Ian Ganly, Laura Fugazzola, Erin Buczek, William C. Faquin, Bryan R. Haugen, Bryan McIver, Caitlin P. McMullen, Kate Newbold, Daniel J. Rocke, Marika D. Russell, Mabel Ryder, Peter M. Sadow, Eric Sherman, Maisie Shindo, David C. Shonk
    JAMA Otolaryngology–Head & Neck Surgery.2024; 150(3): 265.     CrossRef
  • Oncocytic carcinoma of the thyroid: Conclusions from a 20‐year patient cohort
    Nelson R. Gruszczynski, Shahzeb S. Hasan, Ana G. Brennan, Julian De La Chapa, Adithya S. Reddy, David N. Martin, Prem P. Batchala, Edward B. Stelow, Eric M. Dowling, Katherine L. Fedder, Jonathan C. Garneau, David C. Shonka
    Head & Neck.2024;[Epub]     CrossRef
  • Hurthle cell carcinoma: a rare variant of thyroid malignancy – a case report
    Yuvraj Adhikari, Anupama Marasini, Nawaraj Adhikari, Laxman D. Paneru, Binit Upadhaya Regmi, Manita Raut
    Annals of Medicine & Surgery.2023; 85(5): 1940.     CrossRef
  • Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature
    Costanza Chiapponi, Milan J.M. Hartmann, Matthias Schmidt, Michael Faust, Christiane J. Bruns, Anne M. Schultheis, Hakan Alakus
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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Thyroid
Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway
Jun-Qing Jin, Jeong-Sun Han, Jeonghoon Ha, Han-Sang Baek, Dong-Jun Lim
Endocrinol Metab. 2021;36(5):1095-1110.   Published online October 14, 2021
DOI: https://doi.org/10.3803/EnM.2021.1155
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AbstractAbstract PDFPubReader   ePub   
Background
Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role in EMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells.
Methods
Half maximal inhibitory concentration (IC50) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression of PPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2 expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays.
Results
Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-β1)-induced EMT-associated processes such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasion in BCPAP and K1 cells. LGZ restored TGF-β1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore, LGZ and RGZ suppressed TGF-β1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Although there was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZ was hampered by GW9662, a PPAR-γ antagonist.
Conclusion
LGZ inhibits TGF-β1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.

Citations

Citations to this article as recorded by  
  • Diabetes Mellitus and Thyroid Cancers: Risky Correlation, Underlying Mechanisms and Clinical Prevention
    Rongqian Wu, Junping Zhang, Guilin Zou, Shanshan Li, Jinying Wang, Xiaoxinlei Li, Jixiong Xu
    Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 809.     CrossRef
  • Clinicopathological Evaluation of Papillary Thyroid Microcarcinoma
    Ando Takahito, Kimihito Fujii, Hirona Banno, Masayuki Saito, Yukie Ito, Mirai Ido, Manami Goto, Yukako Mouri, Junko Kousaka, Tsuneo Imai, Shogo Nakano
    Cureus.2024;[Epub]     CrossRef
  • Pioglitazone, a peroxisome proliferator‑activated receptor γ agonist, induces cell death and inhibits the proliferation of hypoxic HepG2 cells by promoting excessive production of reactive oxygen species
    Guohao Huang, Mengfan Zhang, Manzhou Wang, Wenze Xu, Xuhua Duan, Xinwei Han, Jianzhuang Ren
    Oncology Letters.2024;[Epub]     CrossRef
  • The Activation of PPARγ by (2Z,4E,6E)-2-methoxyocta-2,4,6-trienoic Acid Counteracts the Epithelial–Mesenchymal Transition Process in Skin Carcinogenesis
    Enrica Flori, Sarah Mosca, Giorgia Cardinali, Stefania Briganti, Monica Ottaviani, Daniela Kovacs, Isabella Manni, Mauro Truglio, Arianna Mastrofrancesco, Marco Zaccarini, Carlo Cota, Giulia Piaggio, Mauro Picardo
    Cells.2023; 12(7): 1007.     CrossRef
  • Cumulative exposure to metabolic syndrome increases thyroid cancer risk in young adults: a population-based cohort study
    Jinyoung Kim, Kyungdo Han, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
    The Korean Journal of Internal Medicine.2023; 38(4): 526.     CrossRef
  • Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs
    Alessia Greco, Francesca Coperchini, Laura Croce, Flavia Magri, Marsida Teliti, Mario Rotondi
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids
    Salvatore Benvenga, Fausto Famà, Laura Giovanna Perdichizzi, Alessandro Antonelli, Gabriela Brenta, Francesco Vermiglio, Mariacarla Moleti
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Identifying and categorizing compounds that reduce corneal transforming growth factor beta induced protein levels: a scoping review
    Gabriella Guo Sciriha, Janet Sultana, Joseph Borg
    Expert Review of Clinical Pharmacology.2022; 15(12): 1423.     CrossRef
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Thyroid
Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study
Kyungsik Kim, Sun Wook Cho, Young Joo Park, Kyu Eun Lee, Dong-Wook Lee, Sue K. Park
Endocrinol Metab. 2021;36(4):790-799.   Published online August 11, 2021
DOI: https://doi.org/10.3803/EnM.2021.1034
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC).
Methods
A case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression.
Results
Excessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels.
Conclusion
Excessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

Citations

Citations to this article as recorded by  
  • Association between urinary iodine concentration and the risk of papillary thyroid cancer by sex and age: a case–control study
    Yerin Hwang, Hyun-Kyung Oh, Jae Hoon Chung, Sun Wook Kim, Jung-Han Kim, Jee Soo Kim, Myung-Hee Shin
    Scientific Reports.2023;[Epub]     CrossRef
  • Association between iodine nutrition and cervical lymph node metastasis of papillary thyroid microcarcinoma
    Hengqiang Zhao, Jin Hu, Le Cui, Yiping Gong, Tao Huang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Sex-specific Associations between Body Mass Index and Thyroid Cancer Incidence among Korean Adults
    Kyoung-Nam Kim, Kyungsik Kim, Sangjun Lee, Sue K. Park
    Cancer Epidemiology, Biomarkers & Prevention.2023; 32(9): 1227.     CrossRef
  • Nomogram Model Based on Iodine Nutrition and Clinical Characteristics of Papillary Thyroid Carcinoma to Predict Lateral Lymph Node Metastasis
    Junrong Wang, Yuzhang Gao, Yuxuan Zong, Weitong Gao, Xueying Wang, Ji Sun, Susheng Miao
    Cancer Control.2023;[Epub]     CrossRef
  • Content of Copper, Iron, Iodine, Rubidium, Strontium and Zinc in Thyroid Malignant Nodules and Thyroid Tissue adjacent to Nodules
    Vladimir Zaichick, Qiping Dong
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Close layer
Review Article
Thyroid
Current Guidelines for Management of Medullary Thyroid Carcinoma
Mijin Kim, Bo Hyun Kim
Endocrinol Metab. 2021;36(3):514-524.   Published online June 22, 2021
DOI: https://doi.org/10.3803/EnM.2021.1082
  • 19,347 View
  • 1,845 Download
  • 31 Web of Science
  • 36 Crossref
AbstractAbstract PDFPubReader   ePub   
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition are different from those used for well-differentiated thyroid cancer. Since the 2015 American Thyroid Association guidelines for the diagnosis and treatment of MTC, the latest, including the National Comprehensive Cancer Network and European Association for Medical Oncology guidelines have been updated to reflect several recent advances in the management of MTC. Advances in molecular diagnosis and postoperative risk stratification systems have led to individualized treatment and follow-up strategies. Multi-kinase inhibitors, such as vandetanib and cabozantinib, can prolong disease progression-free survival with favorable adverse effects. In addition, potent selective rearranged during transfection (RET) inhibitors (selpercatinib and pralsetinib) have shown a promising efficacy in recent clinical trials. This review summarizes the management of MTC in recent guidelines focused on sporadic MTC.

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Close layer
Original Articles
Thyroid
Evaluation of Iodine Status among Korean Patients with Papillary Thyroid Cancer Using Dietary and Urinary Iodine
Ji Yeon Choi, Joon-Hyop Lee, YoonJu Song
Endocrinol Metab. 2021;36(3):607-618.   Published online June 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1005
  • 4,067 View
  • 127 Download
  • 2 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background
Concerns have been raised regarding thyroid disorders caused by excessive iodine in Koreans, who have iodine-rich diets. This study evaluated iodine status using dietary iodine intake and urinary iodine in papillary thyroid cancer (PTC) patients.
Methods
Dietary data of PTC patients were assessed using a 24-hour recall and food frequency questionnaire (FFQ), and urinary iodine concentrations (UICs) were also obtained. To compare the iodine status of PTC patients, Korean adults with or without thyroid disease from the Korea National Health and Nutrition Examination Survey, which had 24-hour recall data and urinary iodine measurements, were analyzed.
Results
The median daily iodine intake by 24-hour recall was 341.7 μg/day in PTC patients, similar to the levels of other Korean adults. Based on UICs, the prevalence of excessive iodine was 54.4% in PTC patients, which was similar to the prevalence among subjects with thyroid disease (55.4%) but slightly higher than that in subjects without thyroid disease (47.7%). Based on dietary iodine by 24-hour recall, the prevalence of excessive iodine intake was 7.2%, which was higher than that among subjects with (4.4%) or without (3.9%) thyroid disease. The dietary iodine intake based on 24-hour recall was closely correlated with the UIC (r=0.4826) in PTC patients, but dietary iodine by FFQ was not significantly correlated with either 24-hour recall or UIC-based dietary iodine.
Conclusion
Excessive iodine intake was more common in PTC patients than in subjects without thyroid disease. Further longitudinal research is necessary to elucidate the role of dietary iodine in PTC.

Citations

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  • Association between iodine nutrition and cervical lymph node metastasis of papillary thyroid microcarcinoma
    Hengqiang Zhao, Jin Hu, Le Cui, Yiping Gong, Tao Huang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
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    Obin Kwon, Dong Yeob Shin, Eun Jig Lee
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    Xueqi Zhang, Fan Zhang, Qiuxian Li, Chuyao Feng, Weiping Teng
    Frontiers in Nutrition.2022;[Epub]     CrossRef
Close layer
Clinical Study
Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma
Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim
Endocrinol Metab. 2021;36(2):359-364.   Published online March 23, 2021
DOI: https://doi.org/10.3803/EnM.2020.890
Correction in: Endocrinol Metab 2022;37(1):181
  • 6,070 View
  • 208 Download
  • 17 Web of Science
  • 17 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study.
Methods
Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases.
Conclusion
KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Citations

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  • Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines
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Close layer
Clinical Study
Molecular Correlates and Nuclear Features of Encapsulated Follicular-Patterned Thyroid Neoplasms
Chan Kwon Jung, Andrey Bychkov, Dong Eun Song, Jang-Hee Kim, Yun Zhu, Zhiyan Liu, Somboon Keelawat, Chiung-Ru Lai, Mitsuyoshi Hirokawa, Kaori Kameyama, Kennichi Kakudo
Endocrinol Metab. 2021;36(1):123-133.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.860
  • 5,530 View
  • 157 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Assessing nuclear features is diagnostically challenging in the aspect of thyroid pathology. The aim of this study was to determine whether pathologists could distinguish BRAF-like and RAS-like nuclear features morphologically and identify morphological features to differentiate thyroid tumors with RAS-like mutations from encapsulated papillary thyroid carcinoma (PTC) with predominant follicular growth and BRAFV600E mutation.
Methods
Representative whole slide images of 16 encapsulated thyroid tumors with predominant follicular growth were reviewed by 12 thyroid pathologists using a web browser-based image viewer. Total nuclear score was calculated from semi-quantitatively scored eight nuclear features. The molecular profile of RAS and BRAF genes was determined by Sanger sequencing.
Results
Total nuclear score ranging 0 to 24 could differentiate BRAF-like tumors from RAS-like tumors with a cut-off value of score 14. The interobserver agreement was the highest for the assessment of nuclear pseudoinclusions (NPIs) but the lowest for nuclear elongation and sickle-shaped nuclei. NPIs were found in tumors with BRAFV600E mutation, but not in tumors with RAS-like mutations. Total nuclear scores were significantly higher for tumors with BRAFV600E than for those with RAS-like mutations (P<0.001).
Conclusion
Our results suggest that NPIs and high nuclear scores have diagnostic utility as rule-in markers for differentiating PTC with BRAFV600E mutation from benign or borderline follicular tumors with RAS-like mutations. Relaxation of rigid criteria for nuclear features resulted in an overdiagnosis of PTC. Immunostaining or molecular testing for BRAFV600E mutation is a useful adjunct for cases with high nuclear scores to identify true PTC.

Citations

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Clinical Study
Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer
Eun Jeong Ban, Daham Kim, Jin Kyong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Kunhong Kim
Endocrinol Metab. 2021;36(1):96-105.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.819
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker.
Methods
LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results.
Results
LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages.
Conclusion
LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Citations

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