Histological Types Of Thyroid Cancer Research Articles

7466 The Effects Of Various Forms Of Diabetes On Features Of Tumor Aggressiveness In Thyroid Cancer

Abstract Disclosure: R.D. Paparodis: None. E. Karvounis: None. A. Kapezanou: None. S. Livadas: None. G. Simeakis: None. D.P. Askitis: None. I. Androulakis: None. N.G. Angelopoulos: None. D. Zianni: None. A. Rizoulis: None. A. Boniakos: None. I. Perogamvros: None. D. Bantouna: None. J.C. Jaume: None. Introduction: Diabetes has been linked to increased risk for several cancers and aggressiveness of tumor behavior. A link between thyroid cancer and diabetes appears controversial in the literature as of yet. We designed the present study to assess whether autoimmune (type 1 + LADA = DM1) or type 2 diabetes (DM2) are associated with more aggressive thyroid cancers compared to those found in non-diabetic (non-DM) individuals. Methods: We retrospectively reviewed data from patients undergoing thyroid surgery in 10 Endocrinology and Endocrine Surgery Clinics throughout Greece over 2 years. We collected data on history and type of diabetes, pre-existing to the thyroid surgery, its treatments and duration, the preoperative thyroid function tests and the surgical pathology findings. We compared the incidence of various histological types of thyroid cancer and the features of tumor aggressiveness between patients with diabetes and those with normal glucose homeostasis (non-DM) (DM1 vs. DM2 vs. non-DM). Results: Overall, n=808 subjects with thyroid cancer were included: n=571 were females (70.7%), age 47.3 ± 14.3 years, BMI 27.0 ± 5.0 Kg/m2, mean TSH 1.99 ± 2.21 mIU/L; n= 692 were non-DM, n=10 had DM1 and n=107 had DM2. Histology revealed n=5 poorly differentiated / anaplastic, n=13 medullary, n=12 Hürthle cell, n=17 follicular and n=773 papillary thyroid cancers (PTC); n=20 (2.5%) with aggressive histological subtypes of PTC, n=5 (0.6%) with distant metastases (MET), n=199 (24.6%) with extrathyroidal extension (ETE), n=419 (51.9%) with capsular invasion (CI), n=225 (27.8%) with lymph nodes involvement (LNi) and n=23 with cancer recurrence (CR) (2.8%). The incidence of aggressive histological types, CR, MET or number of I-131 treatments were not different between groups (p>0.05). ETE, CI and LNi were significantly more common in non-DM compared to both diabetes groups, while gross ETE was more common in DM2 over DM1 and non-DM (p<0.001). Conclusions: More DM1 than DM2 seem to confer a protective effect on several features of cancer aggressiveness in affected individuals. On the other hand, more DM2 than DM1 seems to significantly promote gross ETE. No effect was observed pertaining to the risk for more aggressive tumors or histological subtypes of PTC. Although aggressiveness of thyroid cancer seems controlled in DM1 and to a lesser degree in DM2 the complex interplay between autoimmunity, hyperglycemia and thyroid cancer biology requires larger sample size to better determine causative effects. Presentation: 6/2/2024

7466 The Effects of Various Forms of Diabetes on Features of Tumor Aggressiveness in Thyroid Cancer

Abstract Disclosure: R.D. Paparodis: None. E. Karvounis: None. A. Kapezanou: None. S. Livadas: None. G. Simeakis: None. D.P. Askitis: None. I. Androulakis: None. N.G. Angelopoulos: None. D. Zianni: None. A. Rizoulis: None. A. Boniakos: None. I. Perogamvros: None. D. Bantouna: None. J.C. Jaume: None. Introduction: Diabetes has been linked to increased risk for several cancers and aggressiveness of tumor behavior. A link between thyroid cancer and diabetes appears controversial in the literature as of yet. We designed the present study to assess whether autoimmune (type 1 + LADA = DM1) or type 2 diabetes (DM2) are associated with more aggressive thyroid cancers compared to those found in non-diabetic (non-DM) individuals. Methods: We retrospectively reviewed data from patients undergoing thyroid surgery in 10 Endocrinology and Endocrine Surgery Clinics throughout Greece over 2 years. We collected data on history and type of diabetes, pre-existing to the thyroid surgery, its treatments and duration, the preoperative thyroid function tests and the surgical pathology findings. We compared the incidence of various histological types of thyroid cancer and the features of tumor aggressiveness between patients with diabetes and those with normal glucose homeostasis (non-DM) (DM1 vs. DM2 vs. non-DM). Results: Overall, n=808 subjects with thyroid cancer were included: n=571 were females (70.7%), age 47.3 ± 14.3 years, BMI 27.0 ± 5.0 Kg/m[2], mean TSH 1.99 ± 2.21 mIU/L; n= 692 were non-DM, n=10 had DM1 and n=107 had DM2. Histology revealed n=5 poorly differentiated / anaplastic, n=13 medullary, n=12 Hürthle cell, n=17 follicular and n=773 papillary thyroid cancers (PTC); n=20 (2.5%) with aggressive histological subtypes of PTC, n=5 (0.6%) with distant metastases (MET), n=199 (24.6%) with extrathyroidal extension (ETE), n=419 (51.9%) with capsular invasion (CI), n=225 (27.8%) with lymph nodes involvement (LNi) and n=23 with cancer recurrence (CR) (2.8%). The incidence of aggressive histological types, CR, MET or number of I-131 treatments were not different between groups (p>0.05). ETE, CI and LNi were significantly more common in non-DM compared to both diabetes groups, while gross ETE was more common in DM2 over DM1 and non-DM (p<0.001). Conclusions: More DM1 than DM2 seem to confer a protective effect on several features of cancer aggressiveness in affected individuals. On the other hand, more DM2 than DM1 seems to significantly promote gross ETE. No effect was observed pertaining to the risk for more aggressive tumors or histological subtypes of PTC. Although aggressiveness of thyroid cancer seems controlled in DM1 and to a lesser degree in DM2 the complex interplay between autoimmunity, hyperglycemia and thyroid cancer biology requires larger sample size to better determine causative effects. Presentation: 6/2/2024

Establishment and validation of a novel risk model based on CD8T cell marker genes to predict prognosis in thyroid cancer by integrated analysis of single-cell and bulk RNA-sequencing.

Papillary thyroid cancer (PTC) is a histological type of thyroid cancer, and CD8T is important for the immune response. The single-cell RNA data were acquired from Gene Expression Omnibus. SingleR package was used for cluster identification, and CellChat was exploited to evaluate the interaction among several cell types. Bulk RNA data obtained from the cancer genome atlas were used for determination of prognosis using Kaplan-Meier and Receiver Operating Characteristic curve. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were applied for assessment of function enrichment. The drug sensitivity was calculated in Gene Set Cancer Analysis. The regulatory network was constructed by STRING and Cytoscape. We identified 23 cell clusters and 10 cell types. Cell communication results showed CD8T cell was vital among all immune cell types. Enrichment analysis found the marker genes of CD8T cell was enriched in some signal pathways related to tumor development. Overall, FAM107B and TUBA4A were considered as hub genes and used to construct a risk model. Most immune checkpoint expressions were upregulated in tumor group. Tumor mutation burden results indicated that prognosis of PTC was not related to the mutation of hub genes. Drug sensitivity analysis showed some drugs could be effectively used for the treatment of PTC, and regulatory network identified some targets for the immunotherapy. A 2-gene model of PTC was developed based on the single-cell RNA and bulk RNA data. Besides, we found CD8T was essential for the immune response in PTC.

The impact of metformin on the development and course of anaplastic thyroid cancer in comparison to other histologic types of thyroid cancer

The impact of metformin on the development and course of anaplastic thyroid cancer in comparison to other histologic types of thyroid cancer

Development of a Clinical-Radiomics Nomogram That Used Contrast-Enhanced Ultrasound Images to Anticipate the Occurrence of Preoperative Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma Patients.

Papillary thyroid carcinoma (PTC) is a prevalent histological type of thyroid cancer; however, noninvasive assessment of cervical lymph node metastasis (LNM) poses a challenge. This study aims to develop a novel clinical-radiomics nomogram that utilizes ultrasound (US) images to predict the presence of cervical LNM metastasis in patients with PTC. A total of 423 patients with PTC were recruited to participate in this study between January 2020 and December 2022, of which 282 were classified into the training group and 141 patients were classified into the validation set. Contrast-enhanced ultrasound (CEUS) and B-mode ultrasound (BMUS) images were subjected to radiomic analysis, leading to the extraction of 912 radiomic features. Thereafter, a radiomics score (Radscore) was developed to effectively integrate the information derived from BMUS and CEUS modalities. Univariate and multivariate backward stepwise logistic regression analysis techniques were used to construct the clinical and clinical-radiomics models, respectively. The findings revealed that the clinical-radiomics nomogram incorporated age, sex, CEUS Radscore, and US-reported LNM as risk factors. The nomogram demonstrated good performance using data from the training (AUC = 0.891) and validation (AUC = 0.870) sets. The decision curve analysis implied that this nomogram exhibited good clinical utility, which was further supported by the results of the calibration curves and Hosmer-Lemeshow test. The CEUS Radscore-based clinical radiomics nomogram could serve as a valuable tool for predicting cervical LNM metastasis in patients with PTC, thereby tailoring individualized treatment strategies for them.

ABCA1-Mediated EMT Promotes Papillary Thyroid Cancer Malignancy through the ERK/Fra-1/ZEB1 Pathway.

Papillary thyroid cancer (PTC) is the most prevalent histological type of thyroid cancer (TC) worldwide. Although tumor metastasis occurs in regional lymph nodes, distant metastasis (DM) may also occur. Radioactive iodine (RAI) therapy is an effective treatment for TC; however, resistance to RAI occurs in patients with DM. Therefore, in this study, we investigated the efficacy of DM-related biomarkers as therapeutic targets for PTC therapy. ABCA1 expression was higher in aggressive BCPAP cells than in other PTC cells in terms of migration and invasion capacity. The knockdown of ABCA1 substantially decreased the expression of the epithelial-mesenchymal transition (EMT) marker, N-cadherin, and EMT regulator (ZEB1), resulting in suppressed migration and invasion of BCPAP cells. ABCA1 knockdown also reduced ERK activity and Fra-1 expression, which correlated with the effects of an ERK inhibitor or siRNA-mediated inhibition of ERK or Fra-1 expression. Furthermore, ABCA1-knocked-down BCPAP cells suppressed cell migration and invasion by reducing Fra-1 recruitment to Zeb1 promoter; lung metastasis was not observed in mice injected with ABCA1-knocked-down cells. Overall, our findings suggest that ABCA1 regulates lung metastasis in TC cells.

A comparative analysis of histologic types of thyroid cancer between career firefighters and other occupational groups in Florida

BackgroundFlorida Firefighters experience a higher risk of thyroid cancer than non-firefighters. This study examines whether the histologic types and tumor stage of thyroid cancer is different among firefighters compared to other occupational groups.MethodsEligible cases were firefighters (n = 120) identified in a linkage of Florida Cancer Data System (FCDS) registry records (1981–2014) and Florida State Fire Marshal’s Office employment and certification records, and non-firefighters classified into: blue-collar (n = 655), service (n = 834), white-collar (n = 4,893), and other (n = 1,789). Differences in thyroid histologic type (papillary, follicular, and rare/other less common forms of thyroid cancer), tumor stage, and age at diagnosis were evaluated using multinomial logistic regression models comparing blue-collar, service, white-collar, and other occupational groups with firefighters. Univariate odds ratios as well as odds ratios adjusted for age, gender, race, tumor stage, and year of diagnosis (aOR) and 95% confidence intervals (95%CI) were reported.ResultsService (aOR = 4.12; 95%CI: 1.25—13.65), white-collar (aOR = 3.51; 95%CI: 1.08—11.36), and blue-collar (aOR = 4.59; 95%CI: 1.40—15.07) workers had significantly higher odds of being diagnosed with rare histologic types of thyroid cancer vs papillary type compared to firefighters. Service (aOR = 0.42; 95%CI: 0.27—0.66), white-collar (aOR = 0.39; 95%CI: 0.26—0.59), blue-collar (aOR = 0.36; 95%CI: 0.23—0.56), and other (aOR = 0.34; 95%CI: 0.22—0.53) occupational groups have a significantly lower odds of being diagnosed with rare vs papillary type at a younger age (30—49 years) vs 50—69 years compared to firefighters. However, stage at diagnosis was not significantly different among occupational groups.ConclusionFirefighters diagnosed with thyroid cancer experience a higher odds of papillary compared to rare histologic types of thyroid cancer relative to other workers; there is no evidence of an increased odds of late-stage diagnosis in firefighters relative to other worker groups. Firefighters may benefit from routine screening and active surveillance of suspected thyroid tumors especially given the excellent treatment outcomes available for those diagnosed with early-stage papillary thyroid tumors.

Cancer rate of Bethesda category II thyroid nodules.

Aim Thyroid nodules are very common and may be found in more than 50% of the population. Fine-needle aspiration cytology (FNAC) of thyroid nodules is a very useful diagnostic tool with high sensitivity and predictive value for diagnosis. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) uses six categories for thyroid cytology reporting (I-nondiagnostic, IIbenign, III-atypia of undetermined significance (AUS)/ follicular lesion of undetermined significance (FLUS), IV-follicular neoplasm/suspicious for follicular neoplasm (SFN), V-suspicious for malignancy, and VI-malignant. Our objective was to determine the malignancy rate in Bethesda II nodules. Methods From June 2010 to May 2020 a retrospective analysis was performed among 1166 patients who underwent thyroid surgery for benign thyroid diseases in our institution. Thyroid cytopathological slides and Ultrasound (US) reports were reviewed and classified according to the BSRTC. Data collected included age, gender, cytological features, and histological type of thyroid cancer. Results During the study period, 44.77% (522/1166) of patients with an FNA categorized as Bethesda II underwent thyroid surgery. Incidental malignancy was found in 1.53% (8/522) cases of Bethesda II. The most common malignant tumour type was papillary thyroid carcinoma. Conclusion The current study demonstrates that incidental thyroid carcinoma can be diagnosed after thyroidectomy even in patients with an FNA categorized as Bethesda II.

Loss of ID3 drives papillary thyroid cancer metastasis by targeting E47-mediated epithelial to mesenchymal transition

Papillary thyroid cancer (PTC) is the main histological type of thyroid cancer and accounts for almost all increased cases worldwide. Patients with PTC exhibit a favorable prognosis, but the fact that PTC is often accompanied by a high prevalence of lymph node metastasis (LNM) means that the overall recurrence-free survival rate in PTC patients is relatively low. Herein, we identified that ID3 expression is subdued in PTC tissues and closely associated with LNM and a poor disease-free survival outcome in PTC patients. The main contributor to this gene repression is the hypermethylation of the CpG island at the promoter of ID3. Besides, we uncovered that a loss of ID3 promotes invasion and migration of PTC cells, while an ectopic overexpression of ID3 inhibits invasion and migration. Mechanistically, ID3 exhibits tumor suppressor functions in PTC cells by interacting with E47 to form heterodimers that prevent E47 binding to CDH1 promoter and maintaining CDH1 transcription and epithelial phenotype in PTC cells. Taken together, our study demonstrates that ID3 plays a tumor suppressor role in PTC and impedes metastasis by inhibiting E47-mediated epithelial to mesenchymal transition.

MiR-181a promotes cell proliferation and migration through targeting KLF15 in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the predominant histological type of thyroid cancer, accounting for 80% of thyroid cancers. MiR-181a is a novel microRNA that is usually upregulated in multiple cancers. This study aims to explore the role and underlying mechanism of miR-181a in PTC. CCK8 and Transwell assays were performed to evaluate cell viability and migration. The mRNA level of miR-181a and KLF15 was calculated by qRT-PCR. The protein level of E-Cadherin, N-Cadherin and GAPDH was evaluated by western blot. Dual luciferase assay was conducted to validate that miR-181a directly targeting the 3'-UTR of KLF15 mRNA in TPC-1 cells. We observed that miR-181a was overexpressed and KLF15 was low expressed in PTC tissues and cell lines. Upregulation of miR-181a or downregulation of KLF15 predicted poor outcomes in PTC patients. MiR-181a improved cell growth of PTC, migration and epithelial-mesenchymal transition (EMT) in TPC-1 cells. KLF15 was a target gene of miR-181a and its expression was mediated by miR-181a. KLF15 partially reversed the facilitating effect of miR-181a on cell proliferation and migration in TPC-1 cells. We discovered that miR-181a served as an oncogene downregulating KLF15, thereby inhibiting cell proliferation, migration and the EMT. These findings demonstrate that miR-181a plays a significant role in PTC progression and could be a therapeutic target for PTC.

Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis.

BackgroundAlthough smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence.MethodsWe performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies.ResultsThe summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902).ConclusionOur results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

Fine-Needle Aspiration Cytology and Histological Types of Thyroid Cancer in the Elderly: Evaluation of 9070 Patients from a Single Referral Centre.

Simple SummaryElderly patients have a high prevalence of thyroid nodules, and their management should consider the presence of comorbidities, which are frequent in this age group. In this retrospective monocentric study, we analyzed data of more than 13,000 nodules in order to highlight differences between the elderly and the general population in terms of cytological and histological diagnoses. Thyroid nodules in the elderly are more often benign than in younger patients. Nevertheless, in case of malignancy, follicular-derived well-differentiated tumors are almost always diagnosed in younger patients. Instead, elderly patients more often have tumors with aggressive histotypes. In addition, even in presence of well-differentiated tumors, elderly patients present a higher rate of high-risk pathological features.Background. The prevalence of thyroid nodules increases with age. Their management takes into account the presence of co-morbidities, which are frequent among the elderly. We sought to highlight the differences between the elderly and the general population in cytological and histological diagnoses. Methods. In this retrospective cohort study, we gathered 13,747 nodule data and compared cytological and histological diagnoses between patients aged over 65 years and a control group. Results. Elderly patients had a higher prevalence of cytologically benign nodules and, consequently, they were less frequently subject to surgery. However, there were no differences in terms of malignancy-risk after surgery. At histology, elderly patients often presented aggressive histology such as medullary thyroid carcinoma, poorly-differentiated and anaplastic cancer, tall cell variant of papillary thyroid carcinoma and Hürthle cell carcinoma. Even in presence of well-differentiated cancer, older patients had higher rates of local invasiveness, lateral lymph node involvement and vascular invasion. Conclusion. Thyroid nodules in elderly patients represent a challenging entity since they are very often benign, but, in case of malignancy, aggressive histotypes and high-risk features are more frequent. Therefore, presurgical characterization of nodules in older patients is crucial and might require strict monitoring.

Eva-1 homolog A promotes papillary thyroid cancer progression and epithelial-mesenchymal transition via the Hippo signalling pathway.

Recently, the incidence of thyroid cancer is increasing worldwide. Papillary thyroid cancer (PTC) is the most common histological type of thyroid cancer. Whole‐transcriptome sequence analysis was performed to further understand the primary molecular mechanisms of the occurrence and progression of PTC. Results showed that Eva‐1 homolog A (EVA1A) may be a potential gene for the PTC‐associated gene in thyroid cancer. In this work, the role of EVA1A expression in thyroid cancer was investigated. Real‐time PCR was performed to detect the expression level of EVA1A in 43 pairs of PTC and four thyroid cancer cell lines. The Cancer Genome Atlas (TCGA) database was used to evaluate the relationship between the expression level of EVA1A and the pathological feature of PTC. The logistic regression analysis of the TCGA data set indicated that the expression of EVA1A was an independent risk factor for tumour, nde and metastasis (TNM) in PTC. This study shows the down‐regulation of EVA1A inhibited the colony formation, proliferation, migration and invasion of PTC cell lines. In the protein level, knockdown of EVA1A can regulate the expression of N‐cadherin, vimentin, Bcl‐xL, Bax, YAP and TAZ. This study indicated that EVA1A was an oncogene associated with PTC.

Dynamin 2 Is Correlated with Recurrence and Poor Prognosis of Papillary Thyroid Cancer.

BackgroundPapillary thyroid cancer (PTC) is the most common histological type of thyroid cancer. Most PTC patients have favorable outcomes, but 10% of patients still have distant metastases at presentation or during follow-up. Dynamin 2 (DNM2) is the only DNM ubiquitously expressed in human tissues, but its expression and clinical significance in PTC is still unknown.Material/MethodsIn our study, we investigated the expression of DNM2 in 112 cases of PTC and classified the patients into low and high expression of DNM2. The clinical significance of DNM2 was evaluated by assessing its correlation with the clinicopathological parameters with the chi-square method. The correlations between DNM2 expression and the disease-free survival rate or overall survival rate were assessed with the Kaplan-Meier method and the log-rank test. The independent prognostic factors of PTC were determined by the Cox-regression hazard model.ResultsPatients with low and high DNM2 expression accounted for 75% and 25% respectively in the 112 patients with PTC. High DNM2 expression was significantly associated with recurrence (P=0.014) and poor prognosis (P=0.004). In addition to tumor stage, DNM2 expression was an independent prognostic biomarker of PTC, indicating an unfavorable prognosis.ConclusionsDNM2 was an independent PTC biomarker indicating more likely recurrence and poorer prognosis. Detecting DNM2 expression may help to select the high-risk patients for adjuvant therapy.

Analysis of Let-7 Family miRNA in Plasma as Potential Predictive Biomarkers of Diagnosis for Papillary Thyroid Cancer

The most common histological type of thyroid cancer is papillary thyroid carcinoma (PTC). Radical resection of the thyroid gland is currently the recommended method of treatment. Almost 75% of thyroidectomies performed just for diagnostic purposes are benign. Thus, the confirmation of innovative and more precise noninvasive biomarkers holds promise for the detection of PTC, which may decrease the number of unnecessary thyroid lobectomies. In this work, using the droplet digital PCR (ddPCR) method, we have analyzed the level of five miRNAs (let-7a, let-7c, let-7d, let-7f, and let-7i) in the plasma of patients with PTC and compared them with those of a healthy control group to investigate whether miRNAs also have value in the management of PTC. Levels of four miRNAs, namely let-7a, let-7c, let-7d, and let-7f, were significantly higher in PTC patients than healthy controls. Thus, the analysis of circulating let-7 can be a useful tool and support the currently used methods for PTC diagnosis. However, our observation requires further research on a larger patient group.

The relationship of thyroid nodule size on malignancy risk according to histological type of thyroid cancer.

Background Although several studies have examined the value of thyroid nodule size as a malignancy predictor, the results are conflicting. Purpose To investigate the relationship between nodule size and malignancy risk and to evaluate the impact of nodule size on the false-negative rate of fine needle aspiration or core needle biopsy according to the histological type of thyroid cancer. Material and Methods From January 2013 to December 2013, 3970 thyroid nodules that underwent ultrasound-guided fine needle aspiration or core needle biopsy were retrospectively reviewed. We assessed the relationship between nodule size and malignancy risk according to histological type of thyroid cancer. In addition, we compared the false-negative rate by thyroid nodule size category. Results Of 3970 thyroid nodules, 1170 nodules were malignant. For papillary thyroid carcinoma, nodule size was inversely related to malignancy risk, whereas in nodules of follicular carcinoma and follicular variant papillary thyroid carcinoma, nodule size was positively related to malignancy risk ( P < 0.001). The false-negative rate tended to increase as nodule size increased ( P = 0.002) for all nodules and the overall false-negative rate was 2.3%. Conclusion Overall, nodule size does not correlate with risk of malignancy, but the relationship between nodule size and malignancy risk depends on the histological type of thyroid cancer.

The profile of thyroid cancer in patients undergoing thyroidectomy at Chris Hani Baragwanath Academic Hospital

The histological type of thyroid cancer in well-resourced countries is predominantly papillary. Follicular carcinoma is predisposed by iodine deficiency that was present the Black population of South Africa until salt iodination in 1995. The aim of this study was to analyse the profile of thyroid cancer in Black South Africans from January 2001 to December 2017 and to identify any temporal changes in thyroid cancer histological subtypes since salt iodination. Histopathological reports of patients who underwent thyroidectomy for cancer at Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between January 2001 and December 2017 were retrospectively assessed. Data captured included name, age, gender, race, the date when the specimen was sent and the detailed histopathological report. Of the 143 thyroidectomies performed for malignancy, papillary thyroid cancer was the predominant type (65%) with a papillary to follicular thyroid cancer ratio of 4:1. Follicular, medullary and anaplastic cancers were 16.8%, 9.8% and 2.8% respectively. The reports were incomplete in 5 cases and there were 3 non-epithelial neoplasms. There is a gradual temporal increase in the frequency of resected papillary cancer over a 16 year period while follicular has remained static. These changes may be attributable to better salt iodination.

EZH2 Overexpression as a Useful Prognostic Marker for Aggressive Behaviour in Thyroid Cancer.

Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes, which are key factors in the regulation of cell proliferation and differentiation. EZH2 is overexpressed in many malignancies. We analyzed EZH2 protein expression levels in different histological subtypes of thyroid cancer to examine its utility as a prognostic factor. We examined EZH2 protein expression by immunohistochemistry in tissue samples from 67 cases of poorly differentiated (PDTC) and 48 cases of anaplastic thyroid carcinoma (ATC), and in samples of adjacent normal and differentiated thyroid carcinoma (DTC). We examined differences in expression of EZH2 among various histological types of thyroid cancer, and the relationship between EZH2 expression and patient outcome. EZH2 protein was expressed in PDTC and ATC, but not in normal thyroid gland or DTC. EZH-positivity increased in the order of DTC, PDTC, and ATC (p<0.01). Higher EZH2 expression correlated with poorer survival in PDTC (p=0.004), and a similar but non-significant trend was observed in ATC (p=0.166). Multivariate analysis identified EZH2 as an independent prognostic factor similar to metastatic status in the Japanese Society of Thyroid Surgery (JSTS) classification of PDTC. EZH2 overexpression is associated with malignant potential in thyroid cancer, and may thus be a useful prognostic marker of aggressive thyroid cancer.

Epidemiological Study of Thyroid Carcinoma Using Principal Component Analysis

In this paper, we present a new epidemiological study of thyroid carcinoma, spread over three years (2005-2008), in a sample of 399 Moroccan patients who underwent total thyroidectomy followed by metabolic radiotherapy with Iodine-131. Indeed, in addition to calculating descriptive statistics, we adopted a classification approach, based on the principal component analysis method, to classify our data. The study focused on three types of the thyroid carcinoma: papillary, follicular and undifferentiated. This method allowed us an epidemiological classification according to four criteria: age, sex, type of carcinoma and the region the subject came from. The results obtained show that papillary carcinoma remains the most dominant form among the three histological types of thyroid cancer, with a high incidence in urban coastal areas. Vesicular carcinoma is also present in these areas with a slightly lower impact. Thus, unlike other cancers, thyroid cancer can be developed in cases of a young age. 54.63% of people affected by this disease are between 20 and 45 years old. Also, this study showed that women with thyroid cancer accounted for 87.97% compared to men (12.03%). Of these, 54.13% are between the ages of 20 and 45, followed by women over the age of 45 (44.44%). While among men, we found that 48.63% of cases are older than 45 years, 47.88% are of average age (between 20 and 45 years) and 3.49% are under 19 years old.

Efficacy of an HSP90 inhibitor, ganetespib, in preclinical thyroid cancer models.

Heat shock protein 90 is a molecular chaperon that maintains the correct folding and function of multiple client proteins. The inhibition of heat shock protein 90, which leads to the simultaneous degradation of multiple proteins involved in oncogenic signaling pathways, has revealed an innovative strategy to treat a variety of cancer types. We evaluated the therapeutic effects of ganetespib, a heat shock protein 90 inhibitor, in treating thyroid cancer. Ganetespib effectively inhibited cell proliferation in a dose-dependent manner in eight cell lines originating from four major histologic types of thyroid cancer (papillary, follicular, anaplastic and medullary). Ganetespib decreased cyclin-dependent kinase 1 and arrested cell cycle progression in G2/M phase. The expression of proteins involved in RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways was also inhibited. The RET level was decreased in a medullary thyroid cancer cell line. Ganetespib increased Bim expression, activated caspase-3 and induced apoptosis. In vivo, ganetespib retarded the tumor growth of anaplastic and medullary thyroid cancer xenografts with acceptable safety profiles. These findings indicate that ganetespib has potential in the treatment of patients with thyroid cancer.