scholarly journals MON-504 VEGFA and VEGFR2 Expression in Different Histological Types of Thyroid Nodules: Could Immunohistochemistry Have a Clinical Utility?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Natassia Elena Bufalo ◽  
Karina Colombera Peres ◽  
Larissa Teodoro ◽  
Paulo Latufi-Filho ◽  
Icleia Siqueira Barreto ◽  
...  

Abstract Vascular endothelial growth factors (VEGFs) are a family of proteins involved in several elements that play an important role in the development of blood vessels. Besides acting in angiogenesis, VEGFA has important roles in chemotaxis, for macrophages and granulocytes, and vasodilation. VEGFA binds to VEGFR2, that acts on the MAPK and PI3K pathways, fundamental pathways for thyroid carcinogenesis. In order to assess the expression of VEGFA and VEGFR2, in different thyroid nodules, we used a Tissue MicroArray including 91 benign (74 females, 16 males, 49.84±12.65years old) and 125 malignant thyroid nodules (97 females, 28 males, 46.57±14.87 years old). Clinical and pathology data were obtained from 47 goiters; 43 follicular adenomas (FA) and a total of 104 papillary thyroid carcinomas (PTC), including 35 classic papillary thyroid carcinomas (CPTC), 30 follicular variant of PTC (FVPTC), 25 oxifilic variant of PTC (OVPTC), 14 tall cell papillary thyroid carcinomas (TCPTC); and 21 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 116.9±70.8 months. VEGFA protein expression did not differentiate benign from malignant thyroid nodules. However, VEGFA was more frequently expressed in the less differentiated thyroid tissues. In fact, 95.8% of the FTC had positive expression. On the contrary, the intensity of this protein expression was progressively lower according to the process of cellular dedifferentiation (Goiter: 21.4%; FA: 16.3%; PTC: 8.7% and FTC: 0.0%; x2 = 0.031). There was no difference in VEGFR2 expression between malignant and benign nodules (x2= 0.108), but this protein showed more intense expression in tissues that also presented Hürthle cells (x2 <0.0001). We were not able to find any correlation, neither of VEGFA nor with VEGFR2 expression, and any other feature of aggressiveness, including invasion, metastasis, lymph node metastasis, and distant metastasis. We conclude that VEGFA and VEGFR2 expression may help identify less differentiated tumors and the analysis of a larger cohort may prove the clinical utility of these markers.

2021 ◽  
Vol 12 ◽  
Author(s):  
Fengkai Fang ◽  
Yi Gong ◽  
Liyan Liao ◽  
Fei Ye ◽  
Zhongkun Zuo ◽  
...  

Partially cystic papillary thyroid carcinomas (PCPTCs) are rarely reported papillary thyroid carcinomas (PTCs) and are usually misdiagnosed as benign nodules. The objective of this study was to provide the various sonographic characteristics of partially cystic thyroid nodules for differentiation between malignant and benign nodules, including those for conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Twenty-three PCPTC patients and 37 nodular goiter patients were enrolled in this study. We evaluated the size, cystic percentage, solid echogenicity, calcification, vascularity, and CEUS parameters for each nodule. The final diagnosis of all patients was confirmed via surgery. Univariate analysis demonstrated that compared with benign nodular goiters, PCPTCs more frequently presented with calcification, hypoechogenicity of the solid part, hypoenhancement, heterogeneous enhancement, centrifugal perfusion, peak intensity index <1, time to peak index ≥1, and area under the curve index <1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that heterogeneous enhancement, centrifugal perfusion, and peak intensity index <1 are independent CEUS characteristics related to malignant PCPTCs and can be used for their differentiation from benign nodular goiters (all p < 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to distinguish malignant PCPTCs from benign thyroid nodules.


2012 ◽  
Vol 167 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Patrizia Agretti ◽  
Eleonora Ferrarini ◽  
Teresa Rago ◽  
Antonio Candelieri ◽  
Giuseppina De Marco ◽  
...  

ObjectiveMicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules.DesignIn this study, we evaluated the expression of seven miRNAs in benign nodules, papillary thyroid carcinomas (PTCs), and undetermined nodules at FNA.MethodsThe prospective study included 141 samples obtained by FNA of thyroid nodules from 138 patients. miRNA expression was evaluated by quantitative RT-PCR and statistical analysis of data was performed. Genetic analysis of codon 600 of BRAF gene was also performed.ResultsUsing data mining techniques, we obtained a criterion to classify a nodule as benign or malignant on the basis of miRNA expression. The decision model based on the expression of miR-146b, miR-155, and miR-221 was valid for 86/88 nodules with determined cytology (97.73%), and adopting cross-validation techniques we obtained a reliability of 78.41%. The prediction was valid for 31/53 undetermined nodules with 16 false-positive and six false-negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules.ConclusionsThe expression profiles of three miRNAs allowed us to distinguish benign from PTC starting from FNA. When the assay was applied to discriminate thyroid nodules with undetermined cytology, a low sensitivity and specificity despite the low number of false-negative predictions was obtained, limiting the practical interest of the method.


2019 ◽  
Vol 19 (7) ◽  
pp. 561-570 ◽  
Author(s):  
Hamidreza Maroof ◽  
Soussan Irani ◽  
Armin Arianna ◽  
Jelena Vider ◽  
Vinod Gopalan ◽  
...  

Background: The clinical pathological features, as well as the cellular mechanisms of miR-195, have not been investigated in thyroid carcinoma. Objective: The aim of this study is to identify the interactions of vascular endothelial growth factor (VEGF), p53 and miR-195 in thyroid carcinoma. The clinical and pathological features of miR-195 were also investigated. Methods: The expression levels of miR-195 were identified in 123 primary thyroid carcinomas, 40 lymph nodes with metastatic papillary thyroid carcinomas and seven non-neoplastic thyroid tissues (controls) as well as two thyroid carcinoma cell lines, B-CPAP (from metastasizing human papillary thyroid carcinoma) and MB-1 (from anaplastic thyroid carcinoma), by the real-time polymerase chain reaction. Using Western blot and immunofluorescence, the effects of exogenous miR-195 on VEGF-A and p53 protein expression levels were examined. Then, cell cycle and apoptosis assays were performed to evaluate the roles of miR-195 in cell cycle progression and apoptosis. Results: The expression of miR-195 was downregulated in majority of the papillary thyroid carcinoma tissue as well as in cells. Introduction of exogenous miR-195 resulted in downregulation of VEGF-A and upregulation of p53 protein expressions. Upregulation of miR-195 in thyroid carcinoma cells resulted in cell cycle arrest. Moreover, we demonstrated that miR-195 inhibits cell cycle progression by induction of apoptosis in the thyroid carcinoma cells. Conclusion: Our findings showed for the first time that miR-195 acts as a tumour suppressor and regulates cell cycle progression and apoptosis by targeting VEGF-A and p53 in thyroid carcinoma. The current study exhibited that miR-195 might represent a potential therapeutic target for patients with thyroid carcinomas having aggressive clinical behaviour.


2012 ◽  
Vol 208 (8) ◽  
pp. 489-492 ◽  
Author(s):  
Priscila Pereira Costa Araujo ◽  
Marjory Alana Marcello ◽  
Alfio Jose Tincani ◽  
Ana Carolina Trindade Guilhen ◽  
Elaine Cristina Morari ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Larissa Teodoro ◽  
Karina Colombera Peres ◽  
Matheus Nascimento ◽  
Elisangela Souza Teixeira ◽  
Icleia Siqueira Barreto ◽  
...  

Abstract Thyroid cancer biology is extremely diverse. While some cases never progress clinically or do so indolently, others evolve aggressively and may even lead to death. Cell adhesion molecules are glycoproteins present in the cell membrane and play an important role in inflammatory and neoplastic diseases by recruiting immune cells to these sites. The aim of the present study was to investigate the role of mRNA expression of SELL, ICAM1 and ITGAL in thyroid tumors and their relationship with lymphocyte infiltration. We evaluated by RT-qPCR technique 191 thyroid nodules including 97 benign (79 females, 17 males; 49.8±12.5 years old) and 94 malignant (71 females, 23 males; 48.3±15.5years old) cases. Clinical and pathology data were obtained from 47 goiters; 50 follicular adenomas (FA); 74 papillary thyroid carcinomas (PTC), including: 29 classic papillary thyroid carcinomas (CPTC), 21 follicular variant of PTC (FVPTC), 12oxifilic variant of PTC (OVPTC), 12 tall cell papillary thyroid carcinomas (TCPTC); and 20 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 78.7±54.2 months. SELL was more expressed in malignant (0.85±1.54 UA) than in benign (0.54±0.71 UA, p=0.0027) nodules. The same occurred with ICAM1 (0.99±1.41 vs. 0.46±0.85, p=0.0001), but not with ITGAL gene expression (1.04±1.63 vs. 0.76±1.21, p=0.2131). In addition, the expression of SELL was different when we compared PTC with FA (0.94±1.62 UA vs. 0.47±0.72 UA, p=0.0018) and FTC with FA (0.82±2.38 UA vs. 0.47±0.72 UA, p=0.0078). ICAM1 expression was lower in goiters (0.46±0.90 UA) when compared with PTC (0.93±1.22 UA, p=0.0030) and FTC (1.03±3.30 UA, p=0.0207). Higher expression of ICAM1 (1.16±3.04 UA vs. 0.52±0.96 UA, p=0.0064) and ITGAL (1.17±1.54 UA vs. 0.49±1.39 UA, p=0.0244) was observed in tumors with lymphocyte infiltrate. Also, ITGAL gene expression was higher in tumors that had distant metastasis at diagnosis (1.53±2.18 UA vs. 0.57±1.10 UA, p=0.0217). We were not able to demonstrate any association between any of the investigated molecules and patients’ outcome. In conclusion, our data suggest that cell adhesion molecules may play an important role in neoplastic thyroid cells proliferation. In addition, our findings show that gene expression of SELL and ICAM1 may assist in the histological characterization of follicular patterned thyroid nodules.


2010 ◽  
Vol 21 (4) ◽  
pp. 250-252 ◽  
Author(s):  
Clarissa A. Cassol ◽  
Miao Guo ◽  
Shereen Ezzat ◽  
Sylvia L. Asa

2021 ◽  
Author(s):  
Anabela Zunino ◽  
Claudia Vazquez ◽  
Laura Delfino ◽  
Adriana Reyes ◽  
Alicia Lowenstein

Abstract Purpose We performed a prospective study in patients with positive thyroid peroxidase antibodies (TPOAb), to describe their ultrasound (US) patterns and the prevalence of thyroid nodules. Methods In 195 consecutive patients, with positive TPOAb, thyroid US was performed by the same physician and equipment and categorized into four echographic patterns (EP). We determined the prevalence of thyroid nodules and their etiology confirmed by cytology or histology. Results The median TPOAb was 526 IUI/ml. EP1 or normal US was present in 9,7%; EP2 or early/indeterminate stage in 29,4%; EP3 or established thyroiditis in 45,4% and EP4 or advanced/late stage in 15,5% of the patients. TPOAb (median = 857 UI / ml) (p = 0.001), TSH and thyroid volume ​​were higher in EP3. A higher degree of fibrosis was associated with TPOAb > 1000 IU/ml(p = 0,003). Thyroid nodules were reported on US at 47,2% of HT. Fine needle aspiration(FNA) was performed in 49/60 nodules. Cytology: BII: 41 patients (83,7%), B V: 1 patient (2%): suspicious for lymphoma; B VI: 3 patients(6,1%) : Papillary thyroid carcinoma. Benign cytology was present in 56% of EP3 (p = 0,048). Conclusions Higher TPOAb, TSH levels, and thyroid volume were associated with EP3. Fibrosis correlated with TPOAb > 1000 IU/ml. In our population, benign nodules were associated with established thyroiditis patterns. The increased inflammation and immunological activity of Hashimoto thyroiditis (HT) could be a favorable environment for growth factors for benign nodular development.


2021 ◽  
Author(s):  
Meihua Jin ◽  
Woo Kyung Lee ◽  
Mi-Hyeon You ◽  
Ahreum Jang ◽  
Sheue-yann Cheng ◽  
...  

Background: Catabolism of serine via serine hydroxymethyltransferase2 (SHMT2) through the mitochondrial one-carbon unit pathway is important in tumorigenesis. Therefore, SHMT2 may play a role in thyroid cancer. Methods: Thyroid tissue samples and The Cancer Genome Atlas (TCGA) database were used to evaluate SHMT2 expression in thyroid tissues and the association with clinical outcomes. Results: SHMT2 protein expression was evaluated in thyroid tissues consisting of 52 benign nodules, 129 papillary thyroid carcinomas (PTC) and matched normal samples, and 20 anaplastic thyroid carcinomas (ATC). ATCs presented the highest (95.0%) positivity of SMHT2 protein expression. PTCs showed the second highest (73.6%) positivity of SHMT2 expression, which was significantly higher than that of benign nodules (19.2%, P =0.016) and normal thyroid tissues (0%, P<0.001). Analysis of TCGA data showed that SHMT2 messenger ribonucleic acid (mRNA) expression was significantly higher in tumors than normal tissues (P<0.001). When we classified thyroid cancer into high and low groups according to SHMT2 mRNA expression levels, the thyroid differentiation score for the high SHMT2 group was significantly lower than that of the low SHMT2 group (P<0.001). There was also a significant correlation between SHMT2 mRNA expression and the stemness index (r=0.41, P<0.001). High SHMT2 group had more advanced TNM stages and shorter progression-free survival rates than low SHMT2 group (P<0.01 and P =0.007, respectively). Conclusion: SHMT2 expression is higher in thyroid cancers than normal or benign tissues and is associated with dedifferentiation and poor clinical outcomes. Thus, SHMT2 might be useful as a diagnostic and prognostic marker for thyroid cancer.


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