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Although CCL17 has been reported to exert a vital role in many cancers, the related studies in the thyroid carcinoma have never reported. As a chemokine, CCL17 plays a positive role by promoting the infiltration of immune cells into the tumor microenviroment (TME) to influence tumor invasion and metastasis. Therefore, this study is aimed to investigate the association of CCL17 level with potential prognostic value on tumor immunity in the thyroid carcinoma (THCA) based on the bioinformatics analysis. GEPIA database was applied to analyze CCL17 mRNA expression in THCA data from TCGA database. Through the collection of the data, totally 500 tumor and 57 normal tissue samples were taken for the study. According to survival status and survival time in 500 tumor samples and CCL17 expression from RNA-seq data, all patients were categorized as high- expression (n = 64) and low-expression (n = 436) groups using X-tile program. Next, the association of CCL17 with survival in the thyroid carcinoma patients was examined by using the Kaplan–Meier plotter database. Then, weighted gene co-expression network (WGCNA) was employed to analyze the 1424 DEGs to classify 9 modules. Besides, STRING database was used to obtain the hub genes. GO and KEGG database were employed to explore blue module genes enrichment situations. In addition, TISIDB was used to analyze the relationship of CCL17 expression with tumor-infiltrating lymphocytes proportion, immunostimulators, and major histocompatibility complexes in THCA. The correlation of CCL17 with 22 TIIC subtypes was evaluated by ESTIMATE and CIBERSORT databases. The association of CCL17 level with gene marker of immune cells in THCA was analyzed by GEPIA and TIMER databases. Finally, immunohistochemistry was applied to validate CCL17 expression in 21 tumor and para-carcinoma tissue samples. CCL17 expression in tumors was significantly up-regulated relative to non-carcinoma samples. Patients from CCL17 high-expression group had significantly decreased overall survival compared with low-expression group, which has a significantly importantly potential prognostic value. Moreover, CCL17 and clinical characteristics were analyzed, suggesting that CCL17 expression significantly increased among patients of advanced stage, with advanced T classification, advanced N classification, and higher CCR4 expression. Based on WGCNA, expression of 1424 DEGs in blue module with 258 genes was negatively related to dismal survival and clinical lymph node metastasis in THCA patients. Moreover, CCR4 and CCL17 genes were identified as hub genes within blue module. CCL17 high-expression had greater ImmuneScore, StromalScore and ESTIMATEScore, while lower TumorPurity compared to the CCL17 low-expression. Then, GO and KEGG database were used to analyze blue module genes enrichment situations. The result showed that genes in blue module were associated with cytokine–cytokine receptor interaction, chemokine, and PI3K − Akt pathways. The results of tumor-infiltrating lymphocytes proportion, immunostimulators, and major histocompatibility complexes were significantly positive in CCL17 high-expression. Our findings showed that B cells naïve, T cells CD4 memory resting, T cells CD8, T cells regulatory (Tregs), and dendritic cells resting were the main immune components of THCA tumor microenvironment (TME). CCL17 high-expression in TC was significantly positively related to expression of immune cell gene markers. The result of immunohistochemistry demonstrated that CCL17 expression in tumor tissues significantly increased compared with para-carcinoma tissues. CCL17 high-expression was significantly positively associated with age and advanced N classification, suggesting that CCL17 could accelerate tumor progression by promoting the lymph node metastasis. CCL17 high-expression in THCA tumor microenvironment (TME) accelerates local infiltration of immune cells and enhances anticancer immunity, resulting in worse survival of patients and exerting potential prognostic value on tumor immunity in THCA. [ABSTRACT FROM AUTHOR]

Thyroglossal duct cysts are the most common form of congenital neck cysts. The incidence of thyroid papillary carcinoma in thyroglossal duct cyst is less than 1%. In most cases, the diagnosis is made postoperatively. We present a 52-year-old male with sonographically confirmed thyroglossal duct cyst with a large dystrophic calcification in the midline just cranial to the thyroid isthmus, which showed suspicious atypical cells in fine needle aspiration cytology. However, clinically and by contrast enhanced computed tomography neck, it was free from its adjacent tissues with no lymph node involvement. Various treatment modalities were reviewed to formulate a plan of treatment for further management of the patient. Some studies considered near total thyroidectomy as treatment of choice, whereas others categorised the patients into groups according to the risk factors involved and suggested Sistrunk’s operation with follow up as the treatment modality in the low-risk group. Present case belonged to low-risk group and so underwent Sistrunk’s operation. Histopathology revealed lesion to be encapsulated papillary thyroid carcinoma. The patient has been on regular follow- up for the last 3 months with no radiological or clinical recurrence. [ABSTRACT FROM AUTHOR]

The incidence of differentiated thyroid cancer has been increasing. Nevertheless, its molecular mechanisms are not well understood. In recent years, extracellular nucleotides and nucleosides have emerged as important modulators of tumor microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5′-nucleotidase (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There are no studies evaluating the expression and functionality of these ectonucleotidases on normal or tumor-derived thyroid cells. Thus, we investigated the ability of thyroid cancer cells to hydrolyze extracellular ATP generating adenosine, and the expression of ecto-enzymes, as compared to normal cells. We found that normal thyroid derived cells presented a higher ability to hydrolyze ATP and higher mRNA levels for ENTDP1-2, when compared to papillary thyroid carcinoma (PTC) derived cells, which had a higher ability to hydrolyze AMP and expressed CD73 mRNA and protein at higher levels. In addition, adenosine induced an increase in proliferation and migration in PTC derived cells, whose effect was blocked by APCP, a non-hydrolysable ADP analogue, which is an inhibitor of CD73. Taken together, these results showed that thyroid follicular cells have a functional purinergic signaling. The higher expression of CD73 in PTC derived cells might favor the accumulation of extracellular adenosine in the tumor microenvironment, which could promote tumor progression. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for thyroid cancer management and treatment. [ABSTRACT FROM AUTHOR]

To assess the role of [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) as a preoperative diagnostic tool in papillary thyroid carcinoma (PTC). From 2011 to 2014, 197 patients with PTC (246 tumor foci in all) underwent FDG-PET. Among these patients, 46 underwent neck dissection for lateral neck metastasis. According to the FDG avidity of the tumor foci or lateral neck metastasis, factors associated with the prognostic value were evaluated by univariate and multivariate logistic regression analyses. Among the 197 patients, 7 (3.6 %) were incidentally found to have non-thyroid origin malignancy. Additionally, 63.0 % (155/246) of PTC foci showed FDG uptake on PET/CT. Univariate analysis showed that the tumor size, the presence of extrathyroidal extension, BRAF mutation, and Hashimoto thyroiditis were associated with FDG avidity. However, except for pathological extrathyroidal extension, the other factors showed statistically significant correlations with FDG avidity ( p < 0.001, p = 0.008, and p = 0.009, respectively). FDG uptake in lateral neck node metastasis showed high specificity and negative predictive value (NPV). In four cases of nonspecific findings on ultrasonography (USG)/CT, FDG avidity was helpful to diagnose the presence of lateral neck metastasis. The maximum standardized uptake value (SUV) of PET/CT was correlated with the maximum diameter of the involved lateral node. FDG avidity did not show any significance in the recurrence-free survival of both the thyroid tumor and lateral neck metastasis. The FDG avidity of PTC did not show prognostic predictive meaning. However, in the case of lateral neck metastasis, FDG avidity showed high sensitivity and NPV, and could provide better information in cases of nonspecific findings on USG and CT. [ABSTRACT FROM AUTHOR]

This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 ( BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F ( MAFF), SRY (sex-determining region Y)-box 4 ( SOX4), and retinoic acid receptor, alpha ( RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate serum calprotectin levels and oxidative stress status in patients with papillary thyroid carcinoma (PTC) and the changes in their levels after total thyroidectomy. The study involved 30 patients with PTC and 30 healthy controls. Blood samples were obtained from the PTC patients before and 1 month after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analysed for calprotectin, total antioxidant status (TAS), total oxidant status (TOS) and lipid hydroperokside (LOOH). The preoperative calprotectin, TOS, OSI and LOOH levels of the patients with PTC were significantly higher compared to those of the control group ( p < 0.001, for each). The levels of calprotectin decreased significantly in patients with PTC after the operation ( p < 0.001), while TAS, TOS and OSI levels remained unchanged ( p = 0.313, p = 0.085 and p = 0.163, respectively). Preoperative serum calprotectin levels were positively correlated with TOS, OSI and LOOH levels and negatively correlated with TAS levels in patients with PTC. In conclusion, serum calprotectin levels is increased in patients with PTC, and calprotectin is positively correlated with TOS and LOOH. Serum calprotectin levels is significantly decreased after total thyroidectomy. [ABSTRACT FROM AUTHOR]

Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) constitutes more than 90 % of the thyroid cancers. MAP kinase/ERK pathway plays an important role in the development of several cancers. BRAF which is a member of Raf-kinase family activates this way. BRAF gene activating mutations lead to neoplastic transformation in thyroid follicle cells. In PTC, this mutation itself is a poor prognostic sign independent of other clinicopathological characteristics. We evaluated BRAF mutation and clinical-pathological characteristics in Turkish population with PTC. We assessed 109 patients with PTC (88 female, 21 male). The average age was 38.7 ± 9.9 (17-71). BRAF mutation was detected using polymerase chain reaction and fluorescent melting curve analysis. The results show that BRAF mutation rate was found in 39.45 % of our patients. We observed that BRAF mutation was significantly higher in men, in tumors larger than 1 cm in size, and in patients with classical PTC. Moreover, statistically significant correlations of BRAF with indicators of tumor aggressiveness such as thyroid capsular invasion, multifocality, lymph node metastasis, and extrathyroidal spread were found. Patient groups below and over the age of 45 did not differ in mutation frequency. Patients with micro-PTC were evaluated separately, it was found that BRAF mutation was more frequent in the classic type and that lymph node metastasis rate significantly increased when the mutation was present. We concluded that BRAF was correlated with indicators of tumor aggressiveness in our study population. This fact is taken into consideration in treatment and follow-up of our patients with PTC and positive BRAF mutation. [ABSTRACT FROM AUTHOR]

This study seeks to determine whether the relative levels of attachment to galectins 1 and 3 of cells from thyroid tissues embedded in paraffin blocks can differentiate thyroid tumors from normal tissues. A total of 48 thyroid paraffin sample blocks from 4 groups of patients were analyzed: 12 samples served as controls, 12 samples were from patients with thyroid adenoma, 12 samples were from patients with thyroid follicular carcinoma, and 12 samples were from patients with thyroid papillary carcinoma. The relative attachment of cells to galectins 1 and 3 antigens was determined using the InnoCyte™ ECM Cell Adhesion kit at different cell sample concentrations. All of the samples from thyroid tissue preparations showed attachment to galectins 1 and 3. The samples from tissues with a diagnosis of adenoma, follicular and papillary carcinoma showed an increased adherence to galectins 1 and 3 relative to the controls. Significant differences were found between the means of the adherent cells from the adenomas compared with the follicular and papillary carcinoma samples. When the outcomes from the galectins 1 and 3 cell surface binding were compared, no statistical differences were found. The cells from adenoma and carcinoma samples show more adhesion to galectins 1 and 3 than cells from the control samples. The samples prepared from follicular and papillary carcinomas show more cells adherent to galectins 1 and 3 than those from the adenomas. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the expressions of oncoproteins and to correlate the results with clinicopathologic parameters in papillary thyroid carcinoma (PTC). Papillary thyroid cancer (PTC) is the most common form and accounts for about 80% of all thyroid cancers. Although PTC generally has a good prognosis, some patients suffer from local recurrence and/or distant metastasis. Oncogenes have reported to be related not only in carcinogenesis but also in tumor prognosis, tumor type, differentiation and site of tumor in epithelial malignant tumors such as thyroid, breast, ovarian, and stomach cancer. This study was planned retrospectively and was performed in 87 patients (47 PTC, 40 benign lesions). The data of clinicopathologic parameters and tissue samples were collected from the archives. Sections stained with H&E were evaluated for each case and after confirming the diagnosis of PTC, oncoprotein expressions were determined by immunohistochemical analysis. The differences of oncoprotein expressions in PTC compared with control group were statistically significant. Cyclin D1 and p53 expressions were significantly increased in PTC. The expressions of bcl-2 and c-erbB-2 in PTC were found as increased, but the correlation between these proteins and poor prognostic parameters were not significant. We suggest that increased expressions of cyclin D1 and p53 could be used as prognostic factors in patients with PTC. [ABSTRACT FROM AUTHOR]

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Introduction: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Although the clinical course is usually rather benign, a subset of tumors is more aggressive. The ret/PTC oncogene was found only in PTC, with varying frequencies of up to 30%. Recently, two new variants of ret/PTC could be identified in post-Chernobyl PTCs, which raised the possibility that the prevalence of ret/PTC in non-radiation-induced PTCs might be higher than previously described. Normal thyroid cells do not express wild-type ret, but there is evidence that ret activation from any cause, including wild-type ret, occurs in more than a half of papillary tumors. Methods: We used reverse transcription polymerase chain reaction and sequencing to examine wild-type ret and all five forms of ret/PTC known today in 99 PTCs from Hannover, Düsseldorf, Halle and Regensburg. Our method could also detect other variants within the known breakpoint regions. The presence of the ret tyrosine-kinase domain was examined by immunohistochemistry. Results: Seven PTC1-positive tumors and one PTC3-positive tumor (8%), but none with the new variants or other variants of PTC1, 2 or 3 could be detected. Of 43 tumors examined, 20 showed expression of wild-type ret mRNA and staining of ret protein located predominantly to the cell membrane. Conclusion: Variants of ret/PTC do not substantially contribute to non-radiation-related ret/PTC-positive tumors, and the prevalence of ret/PTC in Germany is low in contrast to the high rate of wild-type ret expression. Thus, expression of wild-type ret should be examined for pathogenic, prognostic and possible therapeutic implications. [ABSTRACT FROM AUTHOR]

A 6-year-old boy received renal transplantation and was treated with methylprednisolone, cyclosporine A and mizoribine. He developed Epstein–Barr virus-associated malignant lymphoma at 10 years and thyroid papillary carcinoma at 20 years of age. Chemotherapy for the malignant lymphoma was done after withdrawal of cyclosporine A and mizoribine, and thyroidectomy was performed for thyroid carcinoma. He was well and his serum creatinine was 1.0 mg/dl at 22 years of age. To our knowledge, no pediatric renal transplant recipient who had thyroid carcinoma or two different types of tumor has been reported in Japan. [ABSTRACT FROM AUTHOR]

Struma ovarii is an ovarian teratoma in which thyroid tissue predominates. Malignancy, either papillary or follicular type in struma ovarii is an extremely rare event. We report a case of papillary carcinoma in struma ovarii in a 27-year-old lady who was admitted with an acute pain in the abdomen. She underwent laparoscopic cystectomy, followed by laparoscopic unilateral salpingo-oophorectomy, total thyroidectomy, and iodine-131 treatment on confirmation of the diagnosis of papillary carcinoma in struma ovarii. Malignancy in struma ovarii can be managed satisfactorily with a combination of surgery and treatment options currently available for primary thyroid cancer. Papillary variant has a more favourable prognosis than its follicular counterpart. [ABSTRACT FROM AUTHOR]

The expression of simple mucin-type antigens, Lewis type-1 antigens, and Lewis type-2-related antigens was evaluated by immunohistochemistry in a series of nine fetal thyroid glands. The aim of the study was to establish whether the previously reported expression of carbohydrate antigens in thyroid carcinomas represents a “de novo” expression or a form of the so-called oncofetal expression. We have detected simple mucin-type antigens and Lewis type-2-related antigens in fetal thyroid tissue. Lewis type-1 antigens were not found. Taking the results of this study together with those previously reported, we conclude that the presence of Lewis type 1 antigens in thyroid carcinomas appears to be a “de novo” expression, whereas the constant and strong expression of simple mucin-type antigens and Lewis type-2-related antigens represents a reexpression (oncofetal expression) of antigens already present during fetal life. [ABSTRACT FROM AUTHOR]