Browsing by Author "Savin, Svetlana (35568292500)"

Samples of thyroglobulin (Tg) were isolated from specimens of differentiated thyroid carcinoma of the papillary type and from normal adjacent glandular tissue, and the content of sialic acid was estimated. Also the in vitro incorporation of 14C-sialic acid, in the form of both CMP (cytidine 5'-monophos-pho-) — activated and non-activated N-acetyl-neuraminic acid, into Tg of malignant and morphologically normal thyroid. © 1992, J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York. All rights reserved.

Samples of thyroglobulin (Tg) were isolated from specimens of differentiated thyroid carcinoma of the papillary type and from normal adjacent glandular tissue, and the content of sialic acid was estimated. Also the in vitro incorporation of 14C-sialic acid, in the form of both CMP (cytidine 5'-monophos-pho-) — activated and non-activated N-acetyl-neuraminic acid, into Tg of malignant and morphologically normal thyroid. © 1992, J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York. All rights reserved.

Aim: To gain a better insight into the differences in biological behaviour between papillary microcarcinoma (PMC) and clinically evident papillary thyroid carcinoma (PTC). Methods: Immunohistochemical analysis of apoptosis related molecules (Bcl-2, Bax, p53) and proliferation related marker (PCNA) in 39 archival cases of PMC and 46 cases of PTC. Results: Bcl-2 and Bax were expressed in most PMCs and PTCs. The average Bcl-2 staining score did not differ significantly between PMCs and PTCs (p > 0.05), but the average Bax score was significantly lower in PMCs (p < 0.05). The Bcl-2/Bax ratio was significantly higher in PMCs than in PTCs (p < 0.05). The expression of p53 was similar in PMCs and PTCs, without a correlation with clinical data, but was associated with high Bax expression (p < 0.05) in these cases in both groups. Non-malignant tissue expressed only Bcl-2, but not p53 or Bax. PCNA expression was significantly lower (p < 0.05) in PMC than in PTC and positively correlated with tumour size (p < 0.05). Conclusions: The higher Bcl-2/Bax ratio and lower proliferative activity in PMC suggest differences from PTC in the balance between apoptosis and proliferation. However, the presence of p53 and Bax in PMC indicates malignant potential, and thus PMC should be treated with caution. © 2008 Royal College of Pathologists of Australasia.

Objective. We aimed to investigate the role of caveolin-1 in papillary thyroid carcinoma pathogenesis. Study Design. Case series with chart review. Setting. Institute for the Application of Nuclear Energy. Subjects and Methods. We evaluated the expression of caveolin-1 in papillary thyroid carcinoma (PTC) by Western blot (WB) and compared the findings with immunohistochemical (IHC) expression of both epithelial and stromal caveolin-1 on the corresponding histological specimens. The results were related to clinicopathological features and BRAF mutation status. Results. Caveolin-1 expression was found in malignant thyroid epithelium and more abundantly in tumor stroma but varied in both compartments within and between PTC subtypes. Caveolin-1 expression in the epithelium was more intense in classical PTC than in the other histological types. On the contrary, stromal caveolin-1 expression was stronger in the follicular, solid, and trabecular PTC variants than in classical PTC. Trends for down-regulation of caveolin-1 expression in epithelium and up-regulation in stroma from the classical via follicular to the solid variant were observed. The relation of WB and IHC results with clinicopathological parameters showed lower caveolin-1 tissue content in BRAF mutated tumors (P <.05), a positive correlation of epithelial caveolin-1 expression with lymph node metastasis (P <.05), and a negative association of stromal caveolin-1 expression with the degree of neoplastic infiltration and BRAF status. Conclusion. Altered expression of caveolin-1 in the thyroid epithelial and stromal compartments may be involved in the pathogenesis of PTC. The potential clinical significance of caveolin-1 expression, as well as its relation to BRAF mutation status, deserves further investigation. © 2013 American Academy of Otolaryngology - Head and Neck Surgery Foundation.

We evaluated some proposed molecular thyroid tumor markers: thyroid peroxidase (TPO), galectin-3, cytokeratin-19, and HBME-1, individually and in combination, by immunohistochemistry in a total of 242 archival thyroid tissue sections. The expression of each individual marker was most helpful for the diagnosis of papillary carcinoma and its follicular variant. However, none of them was sensitive and specific enough to discriminate between Hürthle adenoma and carcinoma. Galectin-3 and HBME-1 could be used as single discriminators between follicular thyroid adenoma and carcinoma, but HBME-1 is the better choice. As a single test, all analyzed tumor markers had sufficient power to predict differentiated thyroid cancer, with sensitivities ranging from 66.5% to 82.2%. The sensitivity was improved by using combinations of some proposed markers. Only two antigens, HBME-1 and TPO, had distinct predictive values for different diagnostic alternatives i.e. a sequential combination improved diagnostic accuracy between follicular thyroid adenoma and the follicular variant of papillary thyroid carcinoma to 92.6% and consequently, between overall benign and malignant thyroid tumors to 89.1%. HBME-1 is the most accurate ancillary stain in discriminating well-differentiated thyroid carcinomas from benign tumors, although the addition of TPO did improve accuracy and served as a useful confirmatory marker. © 2011 The Authors. APMIS © 2011 APMIS.

Purpose: Papillary thyroid carcinoma (PTC) has a strong propensity to metastasize to regional lymph nodes which increases the risk of local-regional relapse and affects the course of the disease. Molecular pathogenesis of lymph node metastasis (LNM) is not yet fully understood. Survivin, a multifunctionale molecule involved in apoptosis, proliferation and angiogenesis, and vascular endothelial growth factor-C (VEGF-C) are suggested to be implicated in lymphatic metastases of human malignancies. Materials and Methods: Expression of survivin and VEGF-C was examined by immunohistochemistry and Western blot in 75 cases of PTCs in relation to their LNM status. Additionally, survivin and VEGF-C were immunohistochemically analyzed in 15 primary PTCs paired with their metastatic tissue in lymph nodes. Results: High expression of survivin and VEGF-C was found in 62.7% and 64.0% cases, respectively, with a positive correlation to each other (Spearman's correlation co-efficient = 0.878, P < 0.001). Expression levels of both proteins were significantly higher in patients with LNM than in those without LNM (P < 0.001). The rate of concomitant high expression of survivin and VEGF-C in patients with LNM involvement was 88.9% (P < 0.01). Metastatic tissue in lymph nodes expressed survivin and VEGF-C at the same high extent as their primary tumors. Conclusion: Concomitant high expression of survivin and VEGF-C is closely associated with LNM status of PTC patients, which suggests their cooperation in the metastatic process. Evaluation of survivin and VEGF-C expression could be clinically significant in predicting the metastatic potential of PTC and subsequent treatment and follow-up of these patients. © 2017 Journal of Cancer Research and Therapeutics.

Cytokeratin19 (CK19) has been reported as a useful marker of thyroid tumors. We evaluated its value for differential diagnosis of thyroid neoplastic lesions and assessed its usefulness for predicting aggressive behavior of papillary thyroid carcinomas by correlating immunohistochemical results with clinicopathological features of the patients. A total of 351 thyroid tissue samples included 27 follicular adenomas (FTA), 18 follicular carcinomas (FTC), 147 papillary carcinomas (71 of follicular type-PTCfv and 76 of classical type-PTCcl) and 33 cases of anaplastic carcinoma with 126 adjacent thyroid tissues. Diagnostic usefulness of CK19 was determined by ROC analysis, while its value as a predictive marker of PTC was tested by univariate and multivariate analysis. According to ROC analysis, CK19 can discriminate both types of PTC from other neoplasias of the thyroid gland (p < 0.05). Although greatest accuracy was gained for the identification of PTCcl (91.07 %), this marker was also helpful for distinguishing PTCfv from FTA and FTC (accuracy 71.43 and 65.17 %, respectively). Regarding the univariate set of tests, high expression of CK19 correlated significantly with age, multifocality, extrathyroidal extension, pT status and pTNM stage of PTC (p < 0.05 for all). Multivariate analyses confirmed the significant association of high CK19 expression with extrathyroidal extension of PTC as well as with pTNM stage (p < 0.05 and p < 0.01, respectively). CK19 is a useful marker for the identification of both types of PTC. High expression of this protein predicts the aggressive behavior of PTC and can help in the identification of a particular subgroup of PTC patients with a potentially worse prognosis. © 2012 Springer Science+Business Media New York.

Cytokeratin19 (CK19) has been reported as a useful marker of thyroid tumors. We evaluated its value for differential diagnosis of thyroid neoplastic lesions and assessed its usefulness for predicting aggressive behavior of papillary thyroid carcinomas by correlating immunohistochemical results with clinicopathological features of the patients. A total of 351 thyroid tissue samples included 27 follicular adenomas (FTA), 18 follicular carcinomas (FTC), 147 papillary carcinomas (71 of follicular type-PTCfv and 76 of classical type-PTCcl) and 33 cases of anaplastic carcinoma with 126 adjacent thyroid tissues. Diagnostic usefulness of CK19 was determined by ROC analysis, while its value as a predictive marker of PTC was tested by univariate and multivariate analysis. According to ROC analysis, CK19 can discriminate both types of PTC from other neoplasias of the thyroid gland (p < 0.05). Although greatest accuracy was gained for the identification of PTCcl (91.07 %), this marker was also helpful for distinguishing PTCfv from FTA and FTC (accuracy 71.43 and 65.17 %, respectively). Regarding the univariate set of tests, high expression of CK19 correlated significantly with age, multifocality, extrathyroidal extension, pT status and pTNM stage of PTC (p < 0.05 for all). Multivariate analyses confirmed the significant association of high CK19 expression with extrathyroidal extension of PTC as well as with pTNM stage (p < 0.05 and p < 0.01, respectively). CK19 is a useful marker for the identification of both types of PTC. High expression of this protein predicts the aggressive behavior of PTC and can help in the identification of a particular subgroup of PTC patients with a potentially worse prognosis. © 2012 Springer Science+Business Media New York.

In vitro lysosomal acid protease activity was studied in human papillary thyroid carcinoma (n = 13). As a control, morphologically normal thyroid tissue from the same patient was used in each individual case of carcinoma. Although a marked variation may be observed between individual cases, each examined papillary thyroid carcinoma showed significantly greater activity of acid proteases, both per unit weight of wet thyroid tissue and per unit of lysosomal proteins, in comparison to the corresponding control (range, 24%‐248%). In conclusion, it is suggested that enhanced proteolytic activity of lysosomal acid proteases in papillary carcinoma is probably a result of disturbance in catabolic degradation of the thyroglobulin molecule in malignantly transformed thyroid tissue. Copyright © 1989 American Cancer Society

In vitro lysosomal acid protease activity was studied in human papillary thyroid carcinoma (n = 13). As a control, morphologically normal thyroid tissue from the same patient was used in each individual case of carcinoma. Although a marked variation may be observed between individual cases, each examined papillary thyroid carcinoma showed significantly greater activity of acid proteases, both per unit weight of wet thyroid tissue and per unit of lysosomal proteins, in comparison to the corresponding control (range, 24%‐248%). In conclusion, it is suggested that enhanced proteolytic activity of lysosomal acid proteases in papillary carcinoma is probably a result of disturbance in catabolic degradation of the thyroglobulin molecule in malignantly transformed thyroid tissue. Copyright © 1989 American Cancer Society

Aim To determine whether matrix metalloproteinase-9 (MMP-9) may be a useful adjunctive tool for predicting unfavorable biological behavior of papillary thyroid carcinoma (PTC) by evaluating the expression profile and proteolytic activity of MMP-9 in PTC by different techniques and correlating the findings with clinicopathological prognostic factors. Methods Immunohistochemical localization of MMP-9 was analyzed with antibodies specific for either total or active MMP-9. Activation ratios of MMP-9 were calculated by quantifying gel zymography bands. Enzymatic activity of MMP-9 was localized by in situ zymography after inhibiting MMP-2 activity. Results Immunostaining of total and active MMP-9 was observed in tumor tissue and occasionally in non-neoplastic epithelium. Only active MMP-9 was significantly associated with extrathyroid invasion, lymph-node metastasis, and the degree of tumor infiltration (P < 0.001, P = 0.004, and P < 0.001, respectively). Gelatin zymography revealed a correlation between the MMP-9 activation ratio and nodal involvement, extrathyroid invasion, and the degree of tumor infiltration. In situ zymography showed that gelatinases exerted their activity in tumor parenchymal and stromal cells. Moreover, after application of MMP-2 inhibitor, the remaining gelatinase activity, corresponding to MMP-9, was highest in cancers with the most advanced degree of tumor infiltration. Conclusions This is the first report suggesting that the evaluation of active MMP-9 by immunohistochemistry and determination of its activation ratio by gelatin zymography may be a useful adjunct to the known clinicopathological factors in predicting tumor behavior. Most important, in situ zimography with an MMP-2 inhibitor for the first time demonstrated a strong impact of MMP-9 activity on the degree of tumor infiltration during PTC progression.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have roles in physiological and pathological processes. We evaluated immunohistochemical expression of MMP-2 and TIMP-2 in paraffin sections of 12 human fetal thyroids at mid-term gestation and 79 thyroid tumors of follicular origin. Besides evaluating expression of these proteins during fetal development and neoplastic transformation, we determined whether expression of MMP-2 and TIMP-2 may help to differentiate papillary thyroid carcinoma (PTC) from follicular thyroid adenoma (FTA) and/or peritumoral tissue (PT). We also investigated their relationship with prognostically important clinicopathological parameters of PTC. Immunoreactive MMP-2 and TIMP-2 were found in all fetal thyroid tissues examined. Tumor tissues contained variable amounts of MMP-2 and TIMP-2, with overexpression of these proteins in PTC compared to FTA and PT tissue. According to the statistical analysis, MMP-2 distinguished follicular variant of PTC from FTA and overall PTC from total nonmalignant lesions. In PTC, high MMP-2 expression correlated with lymph node metastasis (P=0.022), while high TIMP-2 expression was positively correlated with tumor size (P=0.049) and extrathyroid invasion (P=0.017). Overall, these results indicate a role for MMP-2 and TIMP-2 in both thyroid development and malignant transformation and suggest that positive immunohistochemistry for MMP-2 and TIMP-2 might support diagnosis of PTC and predict unfavorable biological behavior. © 2011/2012 IOS Press and the authors. All rights reserved.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have roles in physiological and pathological processes. We evaluated immunohistochemical expression of MMP-2 and TIMP-2 in paraffin sections of 12 human fetal thyroids at mid-term gestation and 79 thyroid tumors of follicular origin. Besides evaluating expression of these proteins during fetal development and neoplastic transformation, we determined whether expression of MMP-2 and TIMP-2 may help to differentiate papillary thyroid carcinoma (PTC) from follicular thyroid adenoma (FTA) and/or peritumoral tissue (PT). We also investigated their relationship with prognostically important clinicopathological parameters of PTC. Immunoreactive MMP-2 and TIMP-2 were found in all fetal thyroid tissues examined. Tumor tissues contained variable amounts of MMP-2 and TIMP-2, with overexpression of these proteins in PTC compared to FTA and PT tissue. According to the statistical analysis, MMP-2 distinguished follicular variant of PTC from FTA and overall PTC from total nonmalignant lesions. In PTC, high MMP-2 expression correlated with lymph node metastasis (P=0.022), while high TIMP-2 expression was positively correlated with tumor size (P=0.049) and extrathyroid invasion (P=0.017). Overall, these results indicate a role for MMP-2 and TIMP-2 in both thyroid development and malignant transformation and suggest that positive immunohistochemistry for MMP-2 and TIMP-2 might support diagnosis of PTC and predict unfavorable biological behavior. © 2011/2012 IOS Press and the authors. All rights reserved.

BACKGROUND: Galectin-3, a lectin with specificity for beta galactosides, is believed to be implicated in multiple biological processes through interactions with complementary glycoconjugates. Alterations in galectin-3 expression are observed in a variety of human tumors. In thyroid, this lectin has been found to be highly expressed in malignancies of epithelial origin. We analyzed galectin-3 expression in medullary thyroid carcinoma (MTC). MATERIALS AND METHODS: An immunohistochemical study using monoclonal antibody was performed on paraffin sections of twenty cases of sporadic MTC, comprising ten cases without and ten cases with lymph node metastases at the time of surgery. RESULTS: Positive cytoplasmic staining for galectin-3 was found in 16/20 cases, but varied in intensity and distribution from weak/focal (7/16) to moderate (7/16) or strong (2/16). Advanced stage of MTC (with lymph node metastases at the time of surgery) showed moderate to strong galectin-3 expression more frequently (8/10) than cases without lymph node metastases (1/10). CONCLUSION: These findings suggest that galectin-3 expression is associated with the advanced stage of disease and that this lectin might play a role in the pathobiology of MTC.

Background: Galectin-3 is an endogenous beta-galactoside binding lectin with putative roles in development, immunomodullation, transformation and metastasis. The purpose of this study was to analyze galectin-3 expression in a series of human thyroid neoplastic lesions. Methods. A total of 76 cases, including 47 specimens of thyroid malignancies, 14 follicnlar adenomas and 15 specimens of normal thyroid tissue, were analyzed immunohistochemically using a monoclonal antibody to galectin-3 and avidin-biotin-peroxidase complex (ABC) method. Results: The immunohistochemical staining results showed galectin-3 expession in neoplastic cells of all 20 cases of papillaly carcinoma, 11 out of 15 follicnlar carcinomas, both oxyphilic carcinomas, all 10 anaplastic carcinomas and 5 out of 14 follicular adenomas. Galectin-3 localization was mostly cytoplasmic, but also membraneous or nuclear in some cells. Follicular cells in normal thyroid tissue were negative. Conclusions. The results of this study indicate that galectin-3 gene is expressed at the protein level in most thyroid carcinomas and some adenomas. Galectin-3 expression was not clearlly correlated with histopathological aggressiveness, dedifferentiation state or determination of malignancy of the follicular tumour. The role of galectin-3 in thyroid tumour biology remains to be elucidated.

Background: Galectin-3 is an endogenous beta-galactoside binding lectin with putative roles in development, immunomodullation, transformation and metastasis. The purpose of this study was to analyze galectin-3 expression in a series of human thyroid neoplastic lesions. Methods. A total of 76 cases, including 47 specimens of thyroid malignancies, 14 follicnlar adenomas and 15 specimens of normal thyroid tissue, were analyzed immunohistochemically using a monoclonal antibody to galectin-3 and avidin-biotin-peroxidase complex (ABC) method. Results: The immunohistochemical staining results showed galectin-3 expession in neoplastic cells of all 20 cases of papillaly carcinoma, 11 out of 15 follicnlar carcinomas, both oxyphilic carcinomas, all 10 anaplastic carcinomas and 5 out of 14 follicular adenomas. Galectin-3 localization was mostly cytoplasmic, but also membraneous or nuclear in some cells. Follicular cells in normal thyroid tissue were negative. Conclusions. The results of this study indicate that galectin-3 gene is expressed at the protein level in most thyroid carcinomas and some adenomas. Galectin-3 expression was not clearlly correlated with histopathological aggressiveness, dedifferentiation state or determination of malignancy of the follicular tumour. The role of galectin-3 in thyroid tumour biology remains to be elucidated.

BACKGROUND Fine-needle aspiration (FNA) has been employed for many years for examining thyroid nodules, and the cytology of aspirates is the primary determinant for whether thyroidectomy is indicated. Fifteen to thirty percent of thyroid nodules, not being clearly benign or malignant, fall into an indeterminate category. The main goals of molecular diagnostics for thyroid nodules are to prevent unnecessary surgery in patients with benign nodules and to stop patients with malignant nodules from being subjected to repeated operations. METHODS This study was designed to evaluate the diagnostic utility of 4 markers in thyroid FNA cytology via testing for the BRAF V600E mutation and the expression of microRNA-221, microRNA-222, and galectin-3 protein in FNA samples with indeterminate cytology. RESULTS A predictor model distinguishing benign samples from malignant samples on the basis of the 4 aforementioned markers was formulated. This decision model provided a sensitivity of 73.5%, a specificity of 89.8%, and a diagnostic accuracy of 75.7%. The positive predictive value was 80.6%, and the negative predictive value was 85.5%; this suggested that the prediction had good reliability. CONCLUSIONS One hundred twenty FNA samples were examined, and 62 nodules were classified as benign with the proposed diagnostic algorithm. This resulted in a reduction of the initial 120 patients to 58 and thus decreased by half the number of persons undergoing surgery. Cancer (Cancer Cytopathol) 2015;123:471-9. © 2015 American Cancer Society. Based on the BRAF V600E mutation status, galectin-3 protein expression, and microRNA-221/222 expression, a predictor model distinguishing benign fine-needle aspiration samples with indeterminate cytology from malignant ones has been developed. © 2015 American Cancer Society.

BACKGROUND Fine-needle aspiration (FNA) has been employed for many years for examining thyroid nodules, and the cytology of aspirates is the primary determinant for whether thyroidectomy is indicated. Fifteen to thirty percent of thyroid nodules, not being clearly benign or malignant, fall into an indeterminate category. The main goals of molecular diagnostics for thyroid nodules are to prevent unnecessary surgery in patients with benign nodules and to stop patients with malignant nodules from being subjected to repeated operations. METHODS This study was designed to evaluate the diagnostic utility of 4 markers in thyroid FNA cytology via testing for the BRAF V600E mutation and the expression of microRNA-221, microRNA-222, and galectin-3 protein in FNA samples with indeterminate cytology. RESULTS A predictor model distinguishing benign samples from malignant samples on the basis of the 4 aforementioned markers was formulated. This decision model provided a sensitivity of 73.5%, a specificity of 89.8%, and a diagnostic accuracy of 75.7%. The positive predictive value was 80.6%, and the negative predictive value was 85.5%; this suggested that the prediction had good reliability. CONCLUSIONS One hundred twenty FNA samples were examined, and 62 nodules were classified as benign with the proposed diagnostic algorithm. This resulted in a reduction of the initial 120 patients to 58 and thus decreased by half the number of persons undergoing surgery. Cancer (Cancer Cytopathol) 2015;123:471-9. © 2015 American Cancer Society. Based on the BRAF V600E mutation status, galectin-3 protein expression, and microRNA-221/222 expression, a predictor model distinguishing benign fine-needle aspiration samples with indeterminate cytology from malignant ones has been developed. © 2015 American Cancer Society.

The most common histological variants of papillary thyroid carcinoma (PTC), classical (CPTC) and follicular (FPTC), have different diagnostic features, molecular biology, and prognosis. Matrix metalloproteinase-9 (MMP-9) endopeptidase which degrades the components of the extracellular matrix is essential in the invasive growth and metastasizing of malignant tumors. The serum copper (Cu)/zinc (Zn) ratios are sensitive diagnostic and prognostic indicators in oncology since Cu- and Zn-dependent enzymes play important roles in the genesis and the progression of tumors. The aim of this study was to examine the expressions of MMP-9 in tissues of CPTC and FPTC, as well as to determine the Cu/Zn ratios in the same samples. MMP-9 was determined immunohistochemically, and the concentrations of copper and zinc in thyroid tissue were determined by means of flame atomic absorption spectrometry. The results obtained revealed significantly higher expressions of MMP-9 in CPTC in comparison with FPTC, as well as higher Cu/Zn ratios in CPTC than in FPTC. Thus, determining MMP-9 activities and the Cu/Zn ratios could improve the accuracy of the standard histopathological diagnosis of these two types of PTC. © 2012 Springer Science+Business Media, LLC.

The most common histological variants of papillary thyroid carcinoma (PTC), classical (CPTC) and follicular (FPTC), have different diagnostic features, molecular biology, and prognosis. Matrix metalloproteinase-9 (MMP-9) endopeptidase which degrades the components of the extracellular matrix is essential in the invasive growth and metastasizing of malignant tumors. The serum copper (Cu)/zinc (Zn) ratios are sensitive diagnostic and prognostic indicators in oncology since Cu- and Zn-dependent enzymes play important roles in the genesis and the progression of tumors. The aim of this study was to examine the expressions of MMP-9 in tissues of CPTC and FPTC, as well as to determine the Cu/Zn ratios in the same samples. MMP-9 was determined immunohistochemically, and the concentrations of copper and zinc in thyroid tissue were determined by means of flame atomic absorption spectrometry. The results obtained revealed significantly higher expressions of MMP-9 in CPTC in comparison with FPTC, as well as higher Cu/Zn ratios in CPTC than in FPTC. Thus, determining MMP-9 activities and the Cu/Zn ratios could improve the accuracy of the standard histopathological diagnosis of these two types of PTC. © 2012 Springer Science+Business Media, LLC.