OBJECTIVE: To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. METHOD: Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. RESULT: The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). CONCLUSION EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.
Adenoma ; metabolism ; pathology ; Antigens, CD ; Cadherins ; metabolism ; Carcinoma ; metabolism ; pathology ; Carcinoma, Papillary ; Humans ; Lymphatic Metastasis ; Receptor, EphA2 ; metabolism ; Thyroid Cancer, Papillary ; Thyroid Gland ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology

Targeted gene therapy has become a promising approach for lung cancer treatment. In our previous work, we reported that the targeted expression of microRNA-7 (miR-7) operated by thyroid transcription factor-1 (TTF-1) promoter inhibited the growth of human lung cancer cells in vitro and in vivo; however, the intervention efficiency needed to be further improved. In this study, we identified the core promoter of TTF-1 (from -1299 bp to -871 bp) by 5' deletion assay and screened out the putative transcription factors nuclear factor-1 (NF-1) and activator protein-1 (AP-1). Further analysis revealed that the expression level of NF-1, but not AP-1, was positively connected with the activation of TTF-1 core promoter in human non-small-cell lung cancer (NSCLC) cells. Moreover, the silencing of NF-1 could reduce the expression level of miR-7 operated by TTF-1 core promoter. Of note, we optimized four distinct sequences to form additional NF-1-binding sites (TGGCA) in the sequence of TTF-1 core promoter (termed as ^optTTF-1 promoter), and verified the binding efficiency of NF-1 on the ^optTTF-1 promoter by electrophoretic mobility shift assay (EMSA). As expected, the ^optTTF-1 promoter could more effectively drive miR-7 expression and inhibit the growth of human NSCLC cells in vitro, accompanied by a reduced transduction of NADH dehydrogenase (ubiquinone) 1α subcomplex 4 (NDUFA4)/protein kinase B (Akt) pathway. Consistently, ^optTTF-1 promoter-driven miR-7 expression could also effectively abrogate the growth and metastasis of tumor cells in a murine xenograft model of human NSCLC. Finally, no significant changes were detected in the biological indicators or the histology of some important tissues and organs, including heart, liver, and spleen. On the whole, our study revealed that the optimized TTF-1 promoter could more effectively operate miR-7 to influence the growth of human NSCLC cells, providing a new basis for the development of microRNA-based targeting gene therapy against clinical lung cancer.
Animals ; Humans ; Mice ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/metabolism* ; MicroRNAs/metabolism* ; Nuclear Proteins/metabolism* ; Thyroid Gland/pathology* ; Thyroid Nuclear Factor 1/genetics* ; Transcription Factors/metabolism*

OBJECTIVETo study the clinicopathologic features and differential diagnosis of dyshormonogenetic goiter.

METHODSThe clinical features, histopathologic findings and immunohistochemistry of four cases of dyshormonogenetic goiter were reviewed.

RESULTSAmongst the cases of dyshormonogenetic goiter studied, three were females and one male. The age of disease onset ranged from 6 to 12 years and the age at operation ranged from 13 to 28 years. Three patients presented with symptoms of hypothyroidism and one patient had normal thyroid function. On gross examination, the thyroid was multinodular and covered by fibrous capsule. Histologically, three patterns were observed. The predominant pattern was microfollicular/trabecular, with hyperplastic follicular cells associated with scanty colloid material. The second pattern was macrofollicular, the follicular cells were cuboid in shape, with inconspicuous mitotic figures. The third pattern was microcystic, with papillary component frequently seen. No normal intervening thyroid parenchyma was found. All the patients were on long-term thyroxine replacement therapy after operation and remained well.

CONCLUSIONSDyshormonogenetic goiter is considered as a form of thyroid hyperplasia due to enzymatic defects in hormone synthesis. The architectural polymorphism and cellular atypia may mimic thyroid neoplasms and cause difficulties in differential diagnosis.

Adolescent ; Adult ; Carcinoma, Papillary ; pathology ; Diagnosis, Differential ; Female ; Goiter ; complications ; pathology ; surgery ; Humans ; Hypothyroidism ; complications ; pathology ; surgery ; Male ; Thyroid Gland ; metabolism ; pathology ; surgery ; Thyroid Neoplasms ; pathology ; Thyroidectomy ; Thyroiditis ; pathology ; Thyrotropin ; metabolism ; Young Adult

BACKGROUND: The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status. METHODS: We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40-74 years who participated in an annual health checkup in 2014. RESULTS: In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = - 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = - 0.03, p = 0.525). CONCLUSIONS TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.
Aged ; Cross-Sectional Studies ; Cysts/etiology* ; Female ; Humans ; Hypertension/metabolism* ; Japan ; Male ; Middle Aged ; Thyroid Diseases/etiology* ; Thyroid Gland/pathology* ; Thyrotropin/metabolism*

OBJECTIVETo describe the pathologic features and differential diagnosis of carcinoma showing thymus-like differentiation (CASTLE) of thyroid.

METHODSThe clinical findings, morphologic features and immunohistochemistry (EnVision) of 2 cases of CASTLE were studied.

RESULTSMacroscopically, the tumor appeared as a hard grayish-white and slightly lobulated mass. Histologic examination revealed well-circumscribed islands of tumor cells associated with desmoplastic stroma. The tumor cells were polygonal to spindle in shape and contained lightly eosinophilic cytoplasm, oval nuclei and small distinct nucleoli. The nuclear atypia was mild to moderate and the mitotic count measured 1 to 2 per 10 high-power fields. Immunohistochemical study showed that the tumor cells expressed CD5 and CD117.

CONCLUSIONSCASTLE is a rare type of thyroid carcinoma with distinctive morphologic findings. It needs to be distinguished from undifferentiated thyroid carcinoma, squamous cell thyroid carcinoma, metastatic lymphoepithelioma-like carcinoma and follicular dendritic cell sarcoma. Immunohistochemical staining for CD5 and CD117 is helpful in confirming the diagnosis.

Adult ; Aged ; CD5 Antigens ; metabolism ; Carcinoma ; metabolism ; pathology ; Carcinoma, Squamous Cell ; pathology ; Cell Differentiation ; Diagnosis, Differential ; Female ; Humans ; Male ; Proto-Oncogene Proteins c-kit ; metabolism ; Sarcoma ; pathology ; Thymoma ; metabolism ; pathology ; Thymus Gland ; pathology ; Thymus Neoplasms ; pathology ; Thyroid Gland ; pathology ; Thyroid Neoplasms ; metabolism ; pathology

PURPOSE: We investigated the merit of ultrasound (US) features and BRAF(V600E) mutation as an additional study of cytology and compared the diagnostic performances of cytology alone, cytology with US correlation, cytology with BRAF(V600E) mutation, and a combination of cytology, US, and BRAF(V600E) mutation all together. MATERIALS AND METHODS: This study included 185 patients (mean age, 48.4 years; range 20-77 years) with 191 thyroid nodules who underwent US-guided fine-needle aspiration (FNA) with an additional BRAF(V600E) mutation test. Three radiologists highly experienced in thyroid imaging retrospectively reviewed US images and classified each nodule into two categories (positive for malignancy or negative for malignancy). Interobserver variability (IOV) of US assessment between the three readers was estimated using the generalized kappa statistic of Landis and Koch. We also calculated the diagnostic performances of these studies. RESULTS: There were 131 cases of malignancy (131/191, 68.6%) and 60 cases of benign nodules (60/191, 31.4%). In terms of IOV of US assessment, the generalized kappa value was 0.242, indicating fair agreement was reached. The combination of cytology with BRAF(V600E) showed higher specificity (100%) and positive predictive value (PPV) (100%) compared to the combination of cytology, BRAF(V600E), and US (specificity 28.3%, 66.7%, 68.3%; PPV 74.6%, 86.6%, 86.8%, respectively; p<0.001). However, cytology with BRAF(V600E) showed lower sensitivity (84.7%) than cytology with BRAF(V600E) and US (96.2%, 98.5%, 95.4%, respectively; p<0.001). CONCLUSION: Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAF(V600E) is the most reliable and objective method for diagnosing thyroid malignancy.
Adult ; Aged ; Biological Markers ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/genetics/*ultrasonography ; Cytodiagnosis ; Female ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins B-raf/*genetics ; Retrospective Studies ; Thyroid Gland/metabolism/pathology ; Thyroid Neoplasms/*diagnosis/genetics/*ultrasonography ; Thyroid Nodule/metabolism/pathology ; Young Adult

PURPOSE: We investigated the merit of ultrasound (US) features and BRAF(V600E) mutation as an additional study of cytology and compared the diagnostic performances of cytology alone, cytology with US correlation, cytology with BRAF(V600E) mutation, and a combination of cytology, US, and BRAF(V600E) mutation all together. MATERIALS AND METHODS: This study included 185 patients (mean age, 48.4 years; range 20-77 years) with 191 thyroid nodules who underwent US-guided fine-needle aspiration (FNA) with an additional BRAF(V600E) mutation test. Three radiologists highly experienced in thyroid imaging retrospectively reviewed US images and classified each nodule into two categories (positive for malignancy or negative for malignancy). Interobserver variability (IOV) of US assessment between the three readers was estimated using the generalized kappa statistic of Landis and Koch. We also calculated the diagnostic performances of these studies. RESULTS: There were 131 cases of malignancy (131/191, 68.6%) and 60 cases of benign nodules (60/191, 31.4%). In terms of IOV of US assessment, the generalized kappa value was 0.242, indicating fair agreement was reached. The combination of cytology with BRAF(V600E) showed higher specificity (100%) and positive predictive value (PPV) (100%) compared to the combination of cytology, BRAF(V600E), and US (specificity 28.3%, 66.7%, 68.3%; PPV 74.6%, 86.6%, 86.8%, respectively; p<0.001). However, cytology with BRAF(V600E) showed lower sensitivity (84.7%) than cytology with BRAF(V600E) and US (96.2%, 98.5%, 95.4%, respectively; p<0.001). CONCLUSION: Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAF(V600E) is the most reliable and objective method for diagnosing thyroid malignancy.
Adult ; Aged ; Biological Markers ; Biopsy, Fine-Needle ; Carcinoma/*diagnosis/genetics/*ultrasonography ; Cytodiagnosis ; Female ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins B-raf/*genetics ; Retrospective Studies ; Thyroid Gland/metabolism/pathology ; Thyroid Neoplasms/*diagnosis/genetics/*ultrasonography ; Thyroid Nodule/metabolism/pathology ; Young Adult

BACKGROUNDPrevious studies have suggested that hypothyroidism correlated with coronary heart diseases (CHD) mortality in long-term cohort, but whether the thyroid function status is associated with myocardial injury in acute ST-elevation myocardial infarction (STEMI) has not been investigated sufficiently.

METHODSFive hundred and eighty-two hospitalized patients from January 2010 to December 2011, with the diagnosis of STEMI, were enrolled in this study. All patients underwent testing for thyroid function status, cardiac troponin I (cTnI), cardiac enzymes, C-reactive protein (CRP). We investigated the association between thyroid hormone levels and cardiac markers (creatine kinase-MB and cTnI), and thus evaluated the potential role of thyroid function status in predicting the myocardial injury.

RESULTSThere were 76 patients (13.06%) who had hypothyroidism including low-T3-syndrome (34 patients, 5.84%), subclinical hypothyroidism (28 patients, 4.81%) and clinical hypothyroidism (14 patients, 2.41%). After adjusting for conventional risk factors (age, gender, smoking, diabetes mellitus, dyslipidemia, hypertension), free triiodothyronine (FT3) was significantly and negatively correlated with log-CKMB (r = -0.244, P < 0.001) and log-cTnI (r = -0.290, P < 0.001), indicating that the lower thyroid hormone level correlates with the severer cardiac injury in STEMI patients. FT3 also had a moderate negative correlation with CRP (r = -0.475, P < 0.001), which might indicate that hypothyroidism may activate the inflammation response. No significant correlation was found between other thyroid parameters (TSH, FT4) and cardiac markers.

CONCLUSIONSAs the lower FT3 level correlates with higher level of cardiac markers and lower left ventricular ejection fraction (LVEF), the hypothyroidism may be a predictor for myocardial injury in STEMI. And these results may warrant further study to investigate whether reversing the hypothyroidism could benefit the STEMI patients.

Aged ; C-Reactive Protein ; metabolism ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; Myocardium ; metabolism ; pathology ; Thyroid Gland ; metabolism ; Triiodothyronine ; blood ; Troponin I ; metabolism

OBJECTIVETo assess thyroid disruption induced by sodium pentachlorophenol (PCP) using Organization for Economic Co-operation and Development (OECD) recommended TG 407 method.

METHODSA total of 30 specific pathogen free (SPF) SD adult male and female rats were randomly divided into 3 groups, and treated with water, 0.33 and 30 mg x kg(-1)x d(-1) of PCP-Na by oral gavage for consecutive 28 days, respectively. After final treatment, histological changes of thyroid were observed by hematoxylin-eosin stain, and the levels of thyroid hormones (total thyroxine (TT(4)), free thyroxine (FT(4)), total triiodothyronine (TT(3)), and free triiodothyronine (FT(3))) were determined by radioimmunoassay. The expression levels of thyroid receptors (TRalpha and TRbeta) mRNA and deiodinases (DioI, DioII and DioIII) mRNA in liver were analyzed by RT-PCR.

RESULTSIn high dose group, liver weight coefficient of male and female rats were (4.82 +/- 0.42)% and (4.99 +/- 0.17)%, increased by 36.2% (t = 7.338, P < 0.01) and 41.8% (t = 8.955, P < 0.01), compared to control group ((3.54 +/- 0.14)%, (3.52 +/- 0.19)%), respectively, while the significant changes of kidney or thyroid weight were not observed. In high dose group, the levels of TT(4) and FT(4) in serum of male rats were (64.95 +/- 7.16) nmol/L and (8.16 +/- 2.29) pmol/L, and decreased by 26.6% (t = -3.999, P < 0.01) and 42.3% (t = -4.112, P < 0.01) compared to control group ((88.48 +/- 6.99) nmol/L, (14.13 +/- 1.68) pmol/L). In the same group, FT(4) in serum of female rats was (4.94 +/- 0.89) pmol/L, decreased by 55.5% (t = -3.380, P = 0.012) compared to control group ((11.10 +/- 3.40) pmol/L) and TT(3) and FT(3) in serum of female rats were (1.92 +/- 0.24) nmol/L and (3.05 +/- 0.79) pmol/L, increased by 74.5% (t = 5.263, P < 0.01) and 55.6% (t = 3.495, P < 0.01) compared to control group ((1.10 +/- 0.23) nmol/L, (1.96 +/- 0.32) pmol/L), respectively. PCP-Na didn't affect the expression levels of TRalpha, TRbeta, DioIII mRNA in high dose group, while DioII expression of male rats (0.209 +/- 0.017) down-regulated by 79.2% (t = -5.426, P < 0.01) compared to control group (1.006 +/- 0.137), and DioI expression of female rats (1.844 +/- 0.189) up-regulated by 66.6% (t = 4.359, P < 0.01) compared to control group (1.005 +/- 0.083), indicating DioI and DioII poss different sensitivity to adverse effects induced by PCP-Na between male and female rats. The histopathological results showed that PCP-Na could give rise to hyperplasia of the follicular epithelium cells, and the depletion of colloid. There were no significant changes in serum THs levels and expression of TRalpha, TRbeta, DioI-IIImRNA in low dose group. However, sporadic lymphocytic infiltration, follicles amplification in part and slightly increased in thickness of follicular cells were observed in this group.

CONCLUSIONPCP is a kind of thyroid disrupting chemical.

Animals ; Female ; Liver ; drug effects ; metabolism ; pathology ; Male ; Organ Size ; Pentachlorophenol ; toxicity ; Rats ; Rats, Sprague-Dawley ; Thyroid Gland ; drug effects ; Thyroid Hormones ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

To investigate the effect of serine/threonine-protein kinase B-Raf (BRAF)-activated long-chain non-coding RNA (lncRNA-BANCR) on apoptosis and autophagy in thyroid carcinoma cells and the underlying mechanisms.
 Methods: RT-PCR was used to detect the expression of lncRNA-BANCR in thyroid carcinoma and normal thyroid tissues. The association between lncRNA-BANCR and clinicopathological data was analyzed in patients with thyroid cancer. Cell counting kit-8 (CCK-8) was used to detect the effect of lncRNA-BANCR on the proliferation of thyroid cancer cells. The effect of lncRNA-BANCR on the apoptosis of thyroid carcinoma cells was detected by flow cytometry. Transwell invasion assay was used to detect the effect of lncRNA-BANCR on the invasive ability of thyroid cancer cells. Western blot was used to detect the changes of autophagy proteins LC3-I and LC3-II after the lncRNA-BANCR expression was suppressed.
 Results: Compared with normal thyroid tissues, the expression level of lncRNA-BANCR in thyroid carcinoma tissues was elevated (P<0.05). The expression of lncRNA-BANCR was positively related to the pathological stage of thyroid carcinoma and the lymph node metastasis. Inhibition of lncRNA-BANCR expression attenuated the proliferation and invasion ability of thyroid cancer cells (both P<0.05); but the apoptosis was enhanced (P<0.05); the expression levels of autophagy protein LC3-I and LC3-II were also increased (P<0.05).
 Conclusion: The expression level of lncRNA-BANCR affects the proliferation, invasion and apoptosis of thyroid cancer cells through modulation of autophagy behavior.
Apoptosis ; Autophagy ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; Proto-Oncogene Proteins B-raf ; metabolism ; RNA, Long Noncoding ; metabolism ; Serine ; metabolism ; Threonine ; metabolism ; Thyroid Gland ; cytology ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology