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3 pages, 171 KiB

Open AccessEditorial

Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment

by Vasyl Vasko

Cancers 2023, 15(19), 4762; https://doi.org/10.3390/cancers15194762 - 28 Sep 2023

Viewed by 1029

Abstract

Understanding the molecular processes driving thyroid cancer invasion, metastasis, and resistance to therapy is essential for the advancement of novel treatment approaches [...] Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

Research

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10 pages, 741 KiB

Open AccessArticle

Outcomes of the Tall-Cell Variant of Papillary Thyroid Carcinoma in Patients with Different Ages: A 17-Year Mono-Institutional Experience

by Agnese Proietti, Francesca Signorini, Riccardo Giannini, Anello Marcello Poma, Elisabetta Macerola, Liborio Torregrossa, Gabriele Materazzi, Alessio Basolo, Ferruccio Santini, Rossella Elisei, David Viola, Fulvio Basolo and Clara Ugolini

Cancers 2023, 15(7), 2152; https://doi.org/10.3390/cancers15072152 - 5 Apr 2023

Cited by 5 | Viewed by 4106

Abstract

The tall-cell variant of papillary thyroid carcinoma (TCPTC) is the most common aggressive variant of papillary thyroid carcinoma (PTC) and typically occurs in older patients. In this study, we analyzed retrospectively the largest mono-institutional series of PTCs with tall-cell features (989 patients) over [...] Read more.

The tall-cell variant of papillary thyroid carcinoma (TCPTC) is the most common aggressive variant of papillary thyroid carcinoma (PTC) and typically occurs in older patients. In this study, we analyzed retrospectively the largest mono-institutional series of PTCs with tall-cell features (989 patients) over a 17-year period, re-evaluating tumors based on age at presentation and outcomes in different age groups. We divided patients into three age groups following different criteria (the criterion from the American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) guidelines, criterion for the statistical division into tertiles and adolescent/post-adolescent criterion) to analyze the clinicopathological characteristics in different age groups, especially in terms of recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). We obtained three main results: 1. the population is distributed among the different age groups, and therefore, this type of cancer is not exclusively found among those of an older age; 2. in the RFS analysis, we can see a higher probability of local recurrence in the younger and older groups and, unexpectedly, a lower probability of local recurrence in the “median age” group; and 3. in the DRFS analysis, we can observe a higher probability of distant recurrence in older patients. From a molecular perspective, no significant differences in the mutational status of BRAF were detected according to different age groups, while mutations in the TERT promoter were exclusively present in older patients of all age groups, highlighting the potential prognostic implications of TERT promoter mutations in PTCs. In conclusion, the results of this series confirm that TC morphology alone in PTCs does not have the same negative prognostic significance in the younger population as in the older population. The reason for these different outcomes remains unclear and needs further studies. Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

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17 pages, 751 KiB

Open AccessArticle

Follicular Thyroid Adenoma and Follicular Thyroid Carcinoma—A Common or Distinct Background? Loss of Heterozygosity in Comprehensive Microarray Study

by Martyna Borowczyk, Paula Dobosz, Ewelina Szczepanek-Parulska, Bartłomiej Budny, Szymon Dębicki, Dorota Filipowicz, Elżbieta Wrotkowska, Michalina Oszywa, Frederik A. Verburg, Małgorzata Janicka-Jedyńska, Katarzyna Ziemnicka and Marek Ruchała

Cancers 2023, 15(3), 638; https://doi.org/10.3390/cancers15030638 - 19 Jan 2023

Cited by 2 | Viewed by 2525

Abstract

Pre- and postsurgical differentiation between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC) represents a significant diagnostic challenge. Furthermore, it remains unclear whether they share a common or distinct background and what the mechanisms underlying follicular thyroid lesions malignancy are. The study [...] Read more.

Pre- and postsurgical differentiation between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC) represents a significant diagnostic challenge. Furthermore, it remains unclear whether they share a common or distinct background and what the mechanisms underlying follicular thyroid lesions malignancy are. The study aimed to compare FTA and FTC by the comprehensive microarray and to identify recurrent regions of loss of heterozygosity (LOH). We analyzed formalin-fixed paraffin-embedded (FFPE) samples acquired from 32 Caucasian patients diagnosed with FTA (16) and FTC (16). We used the OncoScan™ microarray assay (Affymetrix, USA), using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP). The total number of LOH was higher in FTC compared with FTA (18 vs. 15). The most common LOH present in 21 cases, in both FTA (10 cases) and FTC (11 cases), was 16p12.1, which encompasses many cancer-related genes, such as TP53, and was followed by 3p21.31. The only LOH present exclusively in FTA patients (56% vs. 0%) was 11p11.2-p11.12. The alteration which tended to be detected more often in FTC (6 vs. 1 in FTA) was 12q24.11-q24.13 overlapping FOXN4, MYL2, PTPN11 genes. FTA and FTC may share a common genetic background, even though differentiating rearrangements may also be detected. Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

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12 pages, 3508 KiB

Open AccessArticle

TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma

by Soji Toda, Shinya Sato, Nao Saito, Kazumasa Sekihara, Ai Matsui, Daisuke Murayama, Hirotaka Nakayama, Nobuyasu Suganuma, Yoichiro Okubo, Hiroyuki Hayashi, Hiroyuki Iwasaki, Yohei Miyagi and Daisuke Hoshino

Cancers 2022, 14(3), 579; https://doi.org/10.3390/cancers14030579 - 24 Jan 2022

Cited by 9 | Viewed by 4269

Abstract

Background: Anaplastic thyroid carcinoma (ATC) is a highly aggressive thyroid tumor with a poor prognosis. However, there are limited choices for ATC treatment. Recently, the effectiveness of antibody–drug conjugates has been demonstrated in various carcinomas. Whether the targets of antibody–drug conjugates are expressed [...] Read more.

Background: Anaplastic thyroid carcinoma (ATC) is a highly aggressive thyroid tumor with a poor prognosis. However, there are limited choices for ATC treatment. Recently, the effectiveness of antibody–drug conjugates has been demonstrated in various carcinomas. Whether the targets of antibody–drug conjugates are expressed in anaplastic thyroid carcinoma remains unclear. Methods: Fifty-four patients with ATC were enrolled in this study. Tissue microarrays were constructed using the archives of formalin-fixed paraffin-embedded tissue blocks. All sections were stained with the following antibody–drug conjugate targets: human epidermal growth factor receptor 2 (HER2), nectin-4, trophoblast cell surface antigen 2 (TROP-2), glycoprotein non-metastatic B (GPNMB), and B7-H3. Results: HER2 was negative in all tissues, whereas GPNMB and B7-H3 were expressed in most ATC tissues. TROP-2 and nectin-4 were expressed in 65% and 59% of ATC tissues, respectively. TROP-2 was expressed at significantly higher levels in ATC undifferentiated from papillary thyroid carcinoma than in ATC undifferentiated from follicular thyroid carcinoma and de novo ATC. In contrast, nectin-4 expression was markedly higher in patients with de novo ATC than in those with papillary and follicular thyroid carcinoma. Conclusions: TROP-2 and nectin-4 are potential therapeutic targets for ATC undifferentiated from papillary thyroid carcinoma and de novo ATC, respectively. GPNMB and B7-H3 potential for treating all types of ATC. Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

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10 pages, 2011 KiB

Open AccessArticle

TNF-α May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis

by Dan Cristian Gheorghe, Marcel Marian Stanciu, Anca Zamfirescu and Adina Elena Stanciu

Cancers 2021, 13(14), 3609; https://doi.org/10.3390/cancers13143609 - 19 Jul 2021

Cited by 5 | Viewed by 2838

Abstract

Autoimmune thyroiditis (AIT) may impair radioiodine (¹³¹I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during ¹³¹I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate [...] Read more.

Autoimmune thyroiditis (AIT) may impair radioiodine (¹³¹I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during ¹³¹I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of ¹³¹I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after ¹³¹I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after ¹³¹I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after ¹³¹I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = −0.62, p < 0.001 and r = −0.58, p < 0.001). Our results demonstrate that TNF-α may exert different antitumor effects in response to ¹³¹I therapy depending on the patient’s immune profile. Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

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10 pages, 595 KiB

Open AccessArticle

The Prognostic Role of Postablative Non-Stimulated Thyroglobulin in Differentiated Thyroid Cancer

by Szabina Szujo, Laszlo Bajnok, Beata Bodis, Zsuzsanna Nagy, Orsolya Nemes, Karoly Rucz and Emese Mezosi

Cancers 2021, 13(2), 310; https://doi.org/10.3390/cancers13020310 - 15 Jan 2021

Cited by 11 | Viewed by 2697

Abstract

Thyroglobulin (Tg) is the most important tumor marker in differentiated thyroid cancer (DTC). The aim of this study was to assess the diagnostic and prognostic roles of postoperative stimulated and postablative lowest, highest, and one-year non-stimulated Tg values obtained during the follow-up of [...] Read more.

Thyroglobulin (Tg) is the most important tumor marker in differentiated thyroid cancer (DTC). The aim of this study was to assess the diagnostic and prognostic roles of postoperative stimulated and postablative lowest, highest, and one-year non-stimulated Tg values obtained during the follow-up of patients with DTC. In this retrospective study, 222 radioiodine-treated, anti-thyroglobulin antibody (TgAb)-negative DTC patients having at least 9 months’ follow-up time were included (172 papillary and 50 follicular cancers; median age: 48 (from 15 to 91) years; female–male ratio: 158/64; median (quartiles) follow-up time: 54 (22–97) months). The 2015 American Thyroid Association guidelines were applied as criteria of the therapeutic response. Postoperative stimulated Tg values had significantly lower diagnostic accuracy than any of the non-stimulated postablative Tg values. One-year non-stimulated Tg had excellent prognostic value for structural disease: a cut-off value of 0.85 ng/mL had an 88.1% diagnostic accuracy. If the Tg value did not decrease below 0.75 ng/mL at any time during follow-up, the risk of residual disease was 25 times higher. The highest non-stimulated Tg during follow-up was the best predictor of residual disease (e.g., a Tg value exceeding 7.7 ng/mL indicated a 30-fold increase in risk). Non-stimulated Tg values measured during follow-up have excellent diagnostic accuracy to predict structural disease in DTC patients. The risk classification of a patient can safely be modified based on even a single Tg measurement. Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

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Review

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20 pages, 475 KiB

Open AccessReview

Impaired Glucose Metabolism, Anti-Diabetes Medications, and Risk of Thyroid Cancer

by Yevgeniya Kushchayeva, Sergiy Kushchayev, Kirk Jensen and Rebecca J. Brown

Cancers 2022, 14(3), 555; https://doi.org/10.3390/cancers14030555 - 22 Jan 2022

Cited by 8 | Viewed by 3401

Abstract

The prevalence of obesity is progressively increasing along with the potential high risk for insulin resistance and development of type 2 diabetes mellitus. Obesity is associated with increased risk of many malignancies, and hyperinsulinemia has been proposed to be a link between obesity [...] Read more.

The prevalence of obesity is progressively increasing along with the potential high risk for insulin resistance and development of type 2 diabetes mellitus. Obesity is associated with increased risk of many malignancies, and hyperinsulinemia has been proposed to be a link between obesity and cancer development. The incidence of thyroid cancer is also increasing, making this cancer the most common endocrine malignancy. There is some evidence of associations between obesity, insulin resistance and/or diabetes with thyroid proliferative disorders, including thyroid cancer. However, the etiology of such an association has not been fully elucidated. The goal of the present work is to review the current knowledge on crosstalk between thyroid and glucose metabolic pathways and the effects of obesity, insulin resistance, diabetes, and anti-hyperglycemic medications on the risk of thyroid cancer development. Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

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Other

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9 pages, 6458 KiB

Open AccessCommentary

Calcium Signaling in the Thyroid: Friend and Foe

by Muhammad Yasir Asghar, Taru Lassila and Kid Törnquist

Cancers 2021, 13(9), 1994; https://doi.org/10.3390/cancers13091994 - 21 Apr 2021

Cited by 6 | Viewed by 3271

Abstract

Calcium signaling participates in a vast number of cellular processes, ranging from the regulation of muscle contraction, cell proliferation, and mitochondrial function, to the regulation of the membrane potential in cells. The actions of calcium signaling are, thus, of great physiological significance for [...] Read more.

Calcium signaling participates in a vast number of cellular processes, ranging from the regulation of muscle contraction, cell proliferation, and mitochondrial function, to the regulation of the membrane potential in cells. The actions of calcium signaling are, thus, of great physiological significance for the normal functioning of our cells. However, many of the processes that are regulated by calcium, including cell movement and proliferation, are important in the progression of cancer. In the normal thyroid, calcium signaling plays an important role, and evidence is also being gathered showing that calcium signaling participates in the progression of thyroid cancer. This review will summarize what we know in regard to calcium signaling in the normal thyroid as, well as in thyroid cancer. Full article

(This article belongs to the Special Issue Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment)

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