PURPOSE: The goal of this study was to validate the ultrasonography (US) and cytopathological features that are used in the diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) and to characterize the role of BRAF(V600E) mutation analysis in the diagnosis of FVPTC. METHODS: From May 2012 to February 2014, 40 thyroid nodules from 40 patients (mean age, 56.2 years; range, 26 to 81 years) diagnosed with FVPTC were included in this study. The US features of the nodules were analyzed and the nodules were classified as probably benign or suspicious for malignancy. Twenty-three thyroid nodules (57.5%) underwent BRAF(V600E) mutation analysis. Clinical information and histopathologic results were obtained by reviewing the medical records of the patients. RESULTS: Thirty nodules (75.0%) were classified as suspicious for malignancy, while 10 (25.0%) were classified as probably benign. Seven of the eight nodules (87.5%) with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) cytology showed suspicious US features, while one of the two nodules (50.0%) with follicular neoplasm cytology presented suspicious US features. Five of the 23 nodules (21.7%) that underwent BRAF(V600E) mutation analysis had positive results, all of which were diagnosed as suspicious for malignancy or malignant based on cytology. None of the nodules with benign, AUS/FLUS, or follicular neoplasm cytology were positive for the BRAF(V600E) mutation. CONCLUSION: US features allow nodules to be classified as suspicious for malignancy, and the presence of suspicious US features in nodules with ambiguous cytology may aid in the diagnosis of FVPTC. BRAF(V600E) mutation analysis is of limited value in the diagnosis of FVPTC.
Biopsy, Fine-Needle ; Carcinoma, Papillary ; Carcinoma, Papillary, Follicular ; Diagnosis ; Humans ; Medical Records ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroid Nodule ; Ultrasonography*

Thyroid carcinoma is the most common endocrine maligancy, and the worldwide incidence has been rising in recent years. Differentiated thyroid carcinoma is the most common thyroid malignancy, which include thyroid papillary carcinoma and follicular thyroid carcinoma, accounting for about 90 percent of thyroid carcinoma incidence. Currently, surgical treatment, iodine radiotherapy and TSH suppressive therapy are the commonly accepted effective treatments for differentiated thyroid carcinoma, and most patients can be cured. But there are still some patients not sensitive to the general treatments, who have lost the treatment of opportunity. Molecular targeted therapy is an agonistic or suppressive treatment for molecular biology targets of malignant tumor, and currently is a frontier research in the field of malignancy treatment. By retrieving and analyzing the related literature of molecular targeted therapy of thyroid carcinoma through PUBMED in the past 5 years, the article introduced the current status of molecular targeted therapy of thyroid carcinoma.
Adenocarcinoma, Follicular ; drug therapy ; Carcinoma ; drug therapy ; Carcinoma, Papillary ; Humans ; Molecular Targeted Therapy ; Thyroid Cancer, Papillary ; Thyroid Neoplasms ; drug therapy

OBJECTIVE: To discuss the meanings of Oct-4's expression in thyroid adenoma, thyroid papillary carcinoma, thyroid follicular carcinoma, and medullary thyroid carcinoma. METHOD: We examined the expression of Oct-4 in 15 thyroid adenoma, 30 thyroid papillary carcinomas, 2 thyroid follicular carcinomas, and 3 medullary thyroid carcinomas using immunofluorescence. RESULT: Oct-4 expression was observed in all the thyroid-related diseases mentioned above. In thyroid papillary carcinomas, the expression of Oct-4 were higher than that in thyroid adenoma, and had no obvious relationship with the patients age, sex, the size and location of tumor and tumor metastasis. CONCLUSION The formation of the thyroid carcinomas may be concerned with the stem cells in thyroid. There are more stem cells in medullary thyroid carcinomas and follicular carcinomas.
Adenocarcinoma, Follicular ; metabolism ; pathology ; Carcinoma, Neuroendocrine ; Carcinoma, Papillary ; metabolism ; pathology ; Humans ; Octamer Transcription Factor-3 ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

Adenocarcinoma, Follicular ; diagnosis ; pathology ; Adenoma ; diagnosis ; pathology ; Carcinoma, Papillary ; diagnosis ; pathology ; Carcinoma, Papillary, Follicular ; diagnosis ; pathology ; Cell Nucleus ; pathology ; Diagnosis, Differential ; Humans ; Neoplasm Invasiveness ; Thyroid Gland ; pathology ; Thyroid Neoplasms ; diagnosis ; pathology ; Thyroid Nodule ; diagnosis ; Thyroiditis ; diagnosis

Adenocarcinoma, Follicular ; classification ; diagnosis ; pathology ; Carcinoma, Papillary ; diagnosis ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Thyroid Neoplasms ; diagnosis ; pathology ; surgery

The molecular approaches to human diseases are receiving greater attention following the completion of the Human Genome Project. Molecular biology techniques are being widely applied to the field of tumor biology, and thyroid carcinomas are not an exception; several genetic alterations have been suggested to play roles in thyroid carcinogenesis and its progression. Malignant tumors arising from thyroid follicular cells can be classified into papillary carcinoma, follicular carcinoma, poorly differentiated carcinoma and anaplastic carcinoma. BRAF mutation, RET/PTC rearrangement and RAS mutation are the suggested molecular causes of papillary thyroid carcinoma (PTC). RAS mutation, PAX8- PPARγ rearrangement, PTEN mutation or methylation, and PIK3CA mutation are known to induce follicular thyroid carcinoma (FTC). Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are related to adding p53 or β-catenin gene alterations to those of papillary or follicular carcinomas. The more aggressive genetic alterations are added stepwise as thyroid tumors advance from differentiated PTC or FTC to less differentiated PDTC and finally to ATC. Studying the molecular mechanisms underlying thyroid carcinogenesis may help overcome the limitations of the current diagnostic methods and this may provide more accurate diagnostic and prognostic tools. Furthermore, research at the molecular level is essential for personalized therapies and creating targeted therapies for thyroid carcinomas.
Adenocarcinoma, Follicular ; Biology ; Carcinogenesis ; Carcinoma ; Carcinoma, Papillary ; Human Genome Project ; Humans ; Methylation ; Molecular Biology ; Oncogenes ; Thyroid Carcinoma, Anaplastic ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: Malignant follicular lesion is not differentiated from benign lesions cytologically. The objective of this study was to assess the rate and the risk of malignancy in thyroid nodules which were cytologically diagnosed as follicular neoplasm by fine-needle aspiration (FNA) cytology. METHODS: All the patients who had undergone surgery with cytological diagnosis of follicular neoplasm from January 1996 through December 2001 in Asan Medical Center were studied retrospectively. Patients' and nodule characteristics were analyzed for factors associated with the presence of cancer. Two hundred and fifteen patients (196 females, 19 males) were included and their mean age was 39.4 years (range: 12~76). RESULTS: About half of the patients (102 out of 215, 47.4%) had malignancy with 29 papillary carcinomas, 57 follicular carcinomas, 15 H rthle cell carcinomas and 1 medullary carcinoma. Previously suggested factors associated with risk for malignancy, such as male gender, large tumor size (> 4 cm) or age of patients (> 45 years), were not associated with increased risk. Diagnosis of H rthle cell neoplasia on FNA was also not associated with increased risk. Only the extremes in age of the patients (below 20 or above 60 years) were associated with increased risk for malignancy. CONCLUSION: In our findings, prevalence of carcinoma in thyroid nodule patients with cytological diagnosis of follicular neoplasm was much higher than those reported. Clinical characteristics, such as male gender, age and nodule size, are not useful predictors for the presence of malignancy. Thyroid nodules with cytological diagnosis of follicular neoplasm warrant immediate surgery.
Adenocarcinoma, Follicular/pathology ; Adenoma, Oxyphilic/pathology ; Adolescent ; Adult ; Age Factors ; Aged ; Biopsy, Needle ; Carcinoma, Medullary/pathology ; Carcinoma, Papillary, Follicular/pathology ; Child ; Female ; Human ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Thyroid Neoplasms/*pathology ; Thyroid Nodule/*pathology ; Thyroidectomy ; Thyroiditis, Autoimmune/pathology

OBJECTIVETo study Twist expression in thyroid papillary carcinoma (PTC) by immunohistochemistry and to assess its usefulness as marker in the differential diagnosis of PTC, follicular adenomas (FA) and benign papillary lesions (BPL).

METHODSFifty cases of PTC, 48 cases of FA and 47 cases of BPL were evaluated using manual tissue chip and SP immunohistochemical stain to detect the expression of Twist and HBME-1, and comparing the staining to that of cytokeratin 19 (CK19).

RESULTSIn PTC, positive rates of Twist, HBME-1 and CK19 were 100% (48/48), 94.0% (47/50) and 78.0% (39/ 50) respectively; in FA, positive rates were 0, 6.7% (3/45) and 0 respectively; in BPL, positive rates were 7.0% (3/34), 2.1% (1/47) and 0, respectively. The differences between PTC and FA and between PTC and BPL were both statistically significant (P = 0. 000). The sensitivity of Twist, HBME-1 and CK19 was 100%, 94.0% and 78.0%; the specifity was 96.4%, 95.7% and 100%; overall accurary was 97.7%, 95.1% and 91.9%, respectively.

CONCLUSIONSPositive rates of Twist is higher than the other markers in PTC. Immunohistochemical staining of Twist has important significance in the differential diagnosis of thyroid lesions. Twist immunohistochemistry maybe helpful in diagnosis and differential diagnosis of PTC.

Adenocarcinoma, Follicular ; metabolism ; Adenocarcinoma, Papillary ; pathology ; Adenoma ; diagnosis ; metabolism ; Biomarkers, Tumor ; immunology ; Carcinoma, Papillary ; diagnosis ; metabolism ; pathology ; Carcinoma, Papillary, Follicular ; metabolism ; Diagnosis, Differential ; Galectin 3 ; genetics ; metabolism ; Immunohistochemistry ; Keratin-19 ; genetics ; Keratins ; genetics ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; Thyroid Neoplasms ; diagnosis ; metabolism ; pathology ; Thyroid Nodule ; pathology ; Twist-Related Protein 1 ; genetics ; metabolism

OBJECTIVE: To explore the significance of p63 expression in thyroid carcinoma, thyroid papillary carcinoma, thyroid follicular carcinoma, squamous cell carcinoma and medullary thyroid carcinoma in order to find the possible causes of such thyroid-related diseases and if there is some kind of relation among them. METHOD: The expression of p63 was examined in 10 thyroid carcinomas, 20 thyroid papillary carcinomas, 4 thyroid follicular carcinomas, 2 squamous cell carcinomas and 2 medullary thyroid carcinomas using direct immunofluorescence. RESULT: It was shown that p63 expressed in all the thyroid-related diseases mentioned above. In squamous cell carcinoma, p63 has the highest expression and the expression of p63 in thyroid papillary carcinoma has no obvious relationship with the patients age, sex, the size and location of tumor and neoplasm metastasis. CONCLUSION The p63 masculine stem cells in thyroid could be one of the causes of some thyroid papillary carcinomas and thyroid follicular carcinomas. Thyroid papillary carcinoma, thyroid follicular carcinoma and squamous cell carcinoma may have similar origins.
Adenocarcinoma, Follicular ; metabolism ; pathology ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Biomarkers, Tumor ; Carcinoma, Medullary ; metabolism ; pathology ; Carcinoma, Papillary ; metabolism ; pathology ; Humans ; Neoplastic Stem Cells ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology ; Trans-Activators ; metabolism ; Transcription Factors ; Tumor Suppressor Proteins ; metabolism

BACKGROUND: Id proteins are a family of helix-loop-helix proteins and are regarded to be negative regulators of cell differentiation. In general, Id-1 and Id-2 expressions are upregulated during tumor development and progression in a variety of neoplasms, and these expressions may be associated with aggressive tumor behavior. However, little is known about the roles of Id-1 and Id-2 in thyroid neoplasms. METHODS: The expressions of Id-1 and Id-2 were assessed immunohistochemically in 310 normal, hyperplastic, and neoplastic thyroid tissues using tissue microarrays. RESULTS: Normal thyroid tissues rarely expressed Id-1 or Id-2. Moreover, whilst Id-1 expression was more elevated in malignant thyroid tissue than in hyperplastic thyroid tissue, Id-2 expression was more variable. No significant differences were observed between histologic subtypes of thyroid carcinomas with respect to Id-1 or Id-2 expression. Follicular adenomas showed higher expressions of Id-1 and Id-2 than thyroid carcinomas. No significant association was found between clinicopathological parameters and Id-1 expression, though Id-2 expression was significantly reduced in metastatic, stage IV tumors. CONCLUSION: The expressions of Id-1 and Id-2 were elevated in hyperplastic and neoplastic thyroid tissues. However, neither appears suitable as a marker of malignancy or an aggressive phenotype, although Id-2 expression in advanced thyroid carcinomas may reflect a favorable prognosis.
Adenocarcinoma, Follicular ; Adenoma ; Carcinoma, Papillary ; Cell Differentiation ; Humans ; Inhibitor of Differentiation Protein 1 ; Inhibitor of Differentiation Protein 2 ; Phenotype ; Prognosis ; Thyroid Gland* ; Thyroid Neoplasms*