• International journal of thyroidology
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• v.11 no.2
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• pp.152-159
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• 2018

Background and Objectives: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). Materials and Methods: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. Results: The PTCs with the $BRAF^{V600E}$ mutation and the coexistence of $BRAF^{V600E}$ and TERT promoter mutations showed significantly lower expression of NIS (p<0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p<0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p<0.001) and negative correlations with expressions of genes involved in ERK signaling (r=-0.164, p<0.001) and GLUT-1 gene (r=-0.204, p<0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. Conclusion: The NIS expression was reduced by the $BRAF^{V600E}$ mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.

• The Korean Journal of Cytopathology
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• v.8 no.2
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• pp.150-154
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• 1997

Lymphoid infiltration can be seen in some lesions such as Hashimoto's thyroiditis, subacute thyroiditis and several neoplasm of the thyroid. In case of malignancy, there are a few reports of lymphoid infiltration in the diffuse sclerosing variant of papillary carcinoma. But heavy lymphoid infiltraton without evidence of sclerosis is uncommon. We experienced a case of papillary oxyphilic carcinoma with massive lymphoid infiltration, which looks like Warihin tumor of salivary gland. However cytological feature of epithelial cells exhibit that of papillary carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3875-3879
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• 2015

Background: The neutrophil/lymphocyte ratio (NLR) is a simple index of systemic inflammatory response, and has been shown to be a prognostic indicator in some types of cancer. Inflammation has been implicated in the initiation and progression of thyroid cancer. The aim of this study was to examine the relationship of NLR with papillary thyroid cancer (PTC) and different benign thyroid pathologies like multinodular goiter (MNG) and lymphocytic thyroiditis (LT). Materials and Methods: We retrospectively evaluated the neutrophil, lymphocyte counts and NLR calculated from these parameters of 232 patients with histologically confirmed as multinodular goiter (group MNG) (n=70), lymphocytic thyroiditis (group LT) (n=97), LT with PTC (group LT-PTC) (n=25) and PTC (group PTC) (n=40). The optimal cut-off value for NLR was determined. Results: NLR level was significantly higher in groups LT-PTC and PTC as compared to groups MNG and LT (p<0.05). NLR of LT subgroups according to TSH levels were not different (p>0.05). When we grouped the patients as benign and malignant according to PTC presence, the optimum NLR cut-off point obtained from ROC analysis was 1.91 (sensitivity 89.0% and specificity 54.5%). Conclusions: Since NLR was significantly elevated in group LT-PTC and group PTC, NLR value may give an opinion as a potential marker in differentiation of benign and malign thyroid disorders. For this purpose a cut-off value of 1.91 for NLR may be accepted.

• Korean Journal of Head & Neck Oncology
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• v.13 no.1
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• pp.16-23
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• 1997

Although normal thyroid epithelial cells do not constitutively express HLA-DR antigen, their expression in wide spread within thyroid glands obtained from the human with autoimmune thyroid disease and with many neoplastic thyroids. We have, therefore, studied immunohistochemically with regard to the expression of HLA-DR antigen of thyroidectomy specimens from 50 patients of various thyroid diseases with use of paraffin-embedded tissue. One or two sections from each case were stained with commercially available mouse monoclonal antibody for class II HLA-DR antigen(HLA-DR/Alpha, DAKO) and examined by semiquantitative counting system for thyrocytes, neoplastic thyrocytes and other cells expressing HLA-DR antigen. All patients with lymphocytic thyroiditis(2/2) and diffuse hyperplasia(Graves' disease)(5/5), most patients with Hashimoto's disease(9/ll) expressed HLA-DR antigens in thyrocyte with abundant HLA-DR expressing lymphocytic infiltrates with lymph follicle formation in its vicinity or adjacent to the lesion. Most patients with papillary carcinoma(9/1l) had HLA-DR antigen detected in malignant thyrocytes ; while follicular carcinoma(0/3) and follicular adenoma(0/5) did not have detactable HLA-DR immunoreactivity. Adenomatous goiter(3/7) had HLA-DR antigen detected focally in lesser than half cases. Conversely, in four papillary carcinomas and three adenomatous goiters, HLA-DR expression of thyrocytes was found in the absence of HLA-DR expressing lymphoid infiltrates. In such cases therefore other factors more than thyroid autoimmunity must be causative for HLA-DR immunoreactivity. The results of this study indicate as follows. 1) The expression of HLA-DR on thyrocytes involved in autoimmune reactions appeared to be secondary to cytokine release from associated lymphocytic infiltrates. 2) Thyrocytes in thyroid lesions with equal degrees of lymphocytic infiltration without HLA­DR expression exhibited no HLA-DR immunoreactivity. 3) In neoplastic thyrocytes, most papillary carcinoma(9/11) exhibited detactable HLA-DR expression, while follicular carcinoma/adenoma(0/3/0/5) exhibited no detactable HLA-DR immunoreactivity which suggest the existence of divergent mechanisms inducing and modulating HLA-DR expression of different types of neoplastic thyrocytes.

• The Korean Journal of Nuclear Medicine
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• v.14 no.2
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• pp.53-60
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• 1980

The radioimmunoassay of TSH (human thyrotropin) was performed by utilizing anti-h-TSH antibody and purified human thyrotropin supplied from Daiichi Radioisotope company in Japan. From Jan. 1978 through Aug. 1980 the serum concentration of TSH was measured on 41 cases with various thyroid diseases, and 22 normal persons. Among 41 cases, 9(22%) were primary hypothyroidism, 17(41%) Graves' disease, 8(20%), subacute or chronic lymphocytic thyroiditis, and 7(17%) nodular goiter. The results were as follows: 1) The normal values of serum TSH in 22 cases of control group were $4.2{\pm}1.7{\mu}U/ml(1.9-7.4{\mu}U/ml)$, which were within normal range in kit used in this study. 2) The serum TSH concentration in 9 cases with primary hypothroidism were $97.1{\pm}116.4{\mu}U/ml(14.0-300{\mu}U/ml)$, which were significantly elevated as compared with normal control values. 3) The serum TSH concentration in 17 cases with Graves' disease were $1.5{\pm}0.6{\mu}U/ml(1.0-2.5{\mu}U/ml)$, which were below than normal control. 4) The serum TSH concentration in 8 cases with subacute or chronic lymphocytic thyroiditis. revealed wide ranges ($1.6-220{\mu}U/ml$) according to the state of thyroid function. 5) The serum TSH values in 7 cases with nodular goiters were $2.3{\pm}2.0{\mu}U/ml$, which were strictly within normal levels. 6) The serum TSH levels were elevated during prolonged treatment with Tapazole (Methimazole) without serial check of the serum TSH concentration in Graves' disease, so the serial measurement of serum TSH concentration was considered of available index of thyroid states.

• The Korean Journal of Nuclear Medicine
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• v.20 no.1
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• pp.67-73
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• 1986

Subclinical hypothyroidism can be defined as an asymptomatic state in which a reduction in thyroid activity has been compensated by an increased TSH output to maintain a euthyroid state. We analysed clinical features, laboratory data, and pathologic findings in 3g cases of subclinical hypothyroidism who were diagnosed at the Dept. of Internal Medicine, Chungnam National University Hospital from Aug. 1984 to June, 1985. 1) The age distribution was from sixteen to sixty-nine and mean a9e was 34.8. Peak incidence was in the 4th decade and 3rd, 5th, 6th decade in order. 2) The sex distribution showed female preponderance with a ratio of 18.5 to 1. 3) The major presenting manifestations were nonspecific ones such as fatigue, indigestion, and anorexia. 4) Physical examination revealed diffuse goiter in 47.6%. Major abnormalities were no gross abnormality (30.9%), nodular goiter and facial edema. 5) There was no significant difference of the basal serum $T_3\;and\;T_4$ concentrations between subclinical hypothyroidism and normal controls (p>0.05). 6) The basal serum TSH concentration of subclinical hypothyroidism $(32.61{\pm}14.95{\mu}U/ml)$ was significantly higher than that of normal controls $(3.92{\pm}1.05{\mu}U/ml)$ (p<0.005). 7) Microsomal antibody was detected in 80.6% and thyroglobulin antibody was detected in 30%. 8) The pathologic findings in 26 cases revealed Hashimoto's thyroiditis in 76.9% (lymphocytic type, 34.6%; oxyphilic type, 26.9%; fibrotic type, 15.4%). The others were adenomatous goiter(15.4%), adenomatous carcinoma (3.8%) and subacute thyroiditis(3.8%).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7425-7432
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• 2014

Aim: To investigate the expression of protein kinase $CK2{\alpha}$ ($CK2{\alpha}$) in human thyroid disease and its relationship with thyroid cancer metastasis. Materials and Methods: Using immunohistochemistry we measured the expression of $CK2{\alpha}$ in 76 benign and malignant human thyroid cancer tissues, including 10 pairs of papillary carcinoma tissues with or without lymph node cancerous metastasis and similarly 10 pairs of lymph nodes. Results: The expression of $CK2{\alpha}$ was found to be higher in thyroid carcinoma cases (papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma) than in ones such as chronic lymphocytic thyroiditis, nodular goiter and adenoma. These findings were also confirmed by RT-PCR and Western blotting. More strikingly, elevated expression of $CK2{\alpha}$ in thyroid papillary carcinoma tissues was not only significantly associated with lymph node cancerous metastasis and clinical stage of thyroid cancers; but also correlated with epithelial-mesenchymal transition (EMT) and high tenascin C (TNC) expression. In addition, EMT and high TNC expression in thyroid carcinoma tissues was significantly associated with lymph node cancerous metastasis. Conclusions: Elevated expression of nuclear $CK2{\alpha}$ is a poor prognosis indicator in lymph node cancerous metastasis of human thyroid cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3361-3363
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• 2015

Background: Despite the majority of papillary thyroid microcarcinoma (PTMC) patients having an excellent prognosis, cervical lymph node metastases are common. The purpose of this study was to investigate the incidence and the predictive risk factors for occult central compartment lymph node metastasis (CLNM) in PTMC patients. Materials and Methods: 178 patients with clinically node-negative (cN0) PTMC undergoing prophylactic central compartment neck dissection in our hospital from January 2008 to Jun 2010 were enrolled. The relationship between CLNM and the clinical and pathological factors such as gender, age, tumor size, tumor number, tumor location, extracapsular spread (ECS), and coexistance of chronic lymphocytic thyroiditis was analyzed. Results: Occult CLNM was observed in 41% (73/178) of PTMC patients. Multivariate analysis showed that male gender, tumor size (${\geq}6mm$) and ECS were independent variables predictive of CLNM in PTMC patients. Conclusions: Male gender, tumor size (${\geq}6mm$) and ECS were risk factors of CLNM. We recommend a prophylactic central lymph node dissection (CLND) should be considered in PTMC patients with such risk factors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5565-5570
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• 2014

Objectives: This study aimed to characterize the histopathological pattern of thyroid lesions among Saudi patients and to highlight the age and gender variations of these lesions as base line data. Materials and Methods: We retrospectively analyzed the data from thyroid specimens received at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia from January 2006 to December 2013. Results: The 292 thyroidectomy specimens received during the study period came from 230 (78.8%) females and 62 (21.2%) males giving a female: male ratio of 3.7:1. Age of the patients ranged from 14 to 95 years with a mean age 39.7 years. Two hundred and eleven (72.3%) cases were found to be non-neoplastic and 81 (27.7%) cases were neoplastic. The non-neoplastic group included: colloid goiter, including both diffuse and nodular goiter (170 cases; 58.2%), nodular hyperplasia (28 cases; 9.6%), Hashimoto/chronic lymphocytic thyroiditis (12 cases; 4.1%), and Grave's disease (1 case; 0.3%). In neoplastic lesions, there were 7 benign tumors and 74 malignant tumors. Among the benign tumors, 5 were follicular adenomas and 2 were Hurthle cell adenomas. Papillary carcinoma was the commonest malignant tumor accounting for 87.8% of all thyroid malignancies, followed by lymphoma, follicular carcinoma and medullary carcinoma. The size of papillary carcinoma was more than 2 cm in 40 cases (76.9%). Conclusions: Non-neoplastic thyroid lesions were more common than neoplastic ones. Colloid goiter was the most common lesion. Follicular adenoma was the commonest benign tumor and papillary carcinoma was the commonest malignant lesion. There appears to be a slightly increased trend of papillary carcinoma diagnosis, most being diagnosed at an advanced stage.

• Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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• v.61 no.11
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• pp.600-604
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• 2018

Background and Objectives This study aimed to identify a reliable preoperative predictive factor for the development of thyroid cancer in patients with atypia of undetermined significance (AUS) identified by fine needle aspiration biopsy (FNAB). Subjects and Method This was a retrospective cohort study. Two hundred and ninety-nine patients diagnosed with AUS by preoperative FNAB who underwent curative thyroid surgery at our institution between September 2005 and February 2014 were analyzed. Clinical, radiological and molecular features were investigated as preoperative predictors for postoperative permanent malignant pathology. Results The final pathologic results revealed 36 benign tumors including nodular hyperplasia, follicular adenoma, adenomatous goiter, nontoxic goiter, and lymphocytic thyroiditis, as well as 263 malignant tumors including 1 follicular carcinoma and 1 invasive follicular carcinoma; the rest were papillary thyroid carcinomas. The malignancy rate was 87.9%. The following were identified as risk factors for malignancy by univariate analysis: $BRAF^{V600E}$ gene mutation, specific ultrasonographic findings including smaller nodule size, low echogenicity of the nodule, and irregular or spiculated margin (p<0.05). Multivariate analysis revealed that only $BRAF^{V600E}$ mutation was a statistically significant risk factor for malignancy (p<0.05). When $BRAF^{V600E}$ mutation was positive, 98.5% of enrolled patients developed malignant tumors. In addition, the diagnostic rate of malignancy in these cases was approximately 16-fold higher than BRAF-negative cases. Conclusion Patients with AUS thyroid nodules should undergo $BRAF^{V600E}$ gene mutation analysis to improve diagnostic accuracy and if the mutation is confirmed, surgery is recommended due to the high risk of malignancy.