Browsing by Author "Paunović, Ivan (55990696700)"

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Primary aldosteronism (PA) is associated with increased prevalence of metabolic disorders (impaired glucose and lipid metabolism and insulin resistance), but also with more frequent cardiovascular, renal and central nervous system complications. Biochemical and clinical parameters were retrospectively analysed for 40 patients with PA caused by aldosterone-producing adenoma (APA) and compared to the control groups of 40 patients with nonfunctioning adrenal adenoma (NFA) and essential hypertension (HT), and 20 patients with adrenal Cushing syndrome (CS) or subclinical CS (SCS). Systolic, diastolic and mean arterial blood pressures were significantly higher in the PA group (p=0.004; p=0.002; p=0.001, respectively) than in NFA+HT group. PA patients had longer hypertension history (p=0.001) than patients with hypercorticism and all had hypokalaemia. This group showed the smallest mean tumour diameter (p<0.001). The metabolic syndrome was significantly less common in the PA group (37.5% vs. 70% in CS+SCS and 65% in NFA+HT group; p=0.015), although there was no significant difference in any of the analysed metabolic parameters between groups. PA group was found to have the most patients with glucose intolerance (81.8%), although the difference was not significant. The mean BMI for all three groups was in the overweight range. Patients with PA had higher microalbuminuria and a higher tendency for cardiovascular, renal and cerebrovascular events, but the difference was not significant. Our results support the importance of the early recognition of primary aldosteronism on the bases of clinical presentation, as well as an increased screening intensity. © 2019 © 2019.

Primary aldosteronism (PA) is associated with increased prevalence of metabolic disorders (impaired glucose and lipid metabolism and insulin resistance), but also with more frequent cardiovascular, renal and central nervous system complications. Biochemical and clinical parameters were retrospectively analysed for 40 patients with PA caused by aldosterone-producing adenoma (APA) and compared to the control groups of 40 patients with nonfunctioning adrenal adenoma (NFA) and essential hypertension (HT), and 20 patients with adrenal Cushing syndrome (CS) or subclinical CS (SCS). Systolic, diastolic and mean arterial blood pressures were significantly higher in the PA group (p=0.004; p=0.002; p=0.001, respectively) than in NFA+HT group. PA patients had longer hypertension history (p=0.001) than patients with hypercorticism and all had hypokalaemia. This group showed the smallest mean tumour diameter (p<0.001). The metabolic syndrome was significantly less common in the PA group (37.5% vs. 70% in CS+SCS and 65% in NFA+HT group; p=0.015), although there was no significant difference in any of the analysed metabolic parameters between groups. PA group was found to have the most patients with glucose intolerance (81.8%), although the difference was not significant. The mean BMI for all three groups was in the overweight range. Patients with PA had higher microalbuminuria and a higher tendency for cardiovascular, renal and cerebrovascular events, but the difference was not significant. Our results support the importance of the early recognition of primary aldosteronism on the bases of clinical presentation, as well as an increased screening intensity. © 2019 © 2019.

Objectives: Papillary thyroid carcinoma (PTC) usually has a good prognosis, but some patients develop an aggressive course of the disease, leading to a poor outcome. Vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 9 (MMP-9) have been shown to play roles in tumor progression in various human malignancies. Methods: We analyzed VEGF-C and active MMP-9 expression profiles in PTC samples using immunohistochemistry and Western blotting. Results: Immunohistochemistry showed positive staining for VEGF-C and active MMP-9 in 83% and 57% of PTCs, respectively (n=60), with a positive correlation between their expression levels (Spearman, P <.001). Concomitant high expression of VEGF-C and active MMP-9 correlated with the presence of lymph node metastasis (P =.005), pT status (P =.004), pTNM tumor stage (P =.005), and particularly the degree of tumor infiltration (P <.001, Fisher exact test). Densitometric analysis of Western blot bands confirmed correlation between VEGF-C and active MMP-9 expression (Wilcoxon and Spearman tests) and significant association with the clinicopathologic parameters (Mann-Whitney and Kruskal-Wallis tests). Conclusions: Association of coexpressed high levels of VEGF-C and active MMP-9 with lymphatic spreading and local invasiveness of PTC suggests their potential usefulness as predictive biomarkers of aggressive PTC behavior. © American Society for Clinical Pathology, 2016. All rights reserved.

Pheochromocytoma (PCC) is an unusual benign adrenal tumor with an unexamined status of the elements. This study delivers the first insight into the levels of microelements (Mn, Co, Cu, Zn, As, Se, Th), toxic elements (Cd, Pb, U), and macroelements (Na, K, Mg, Ca) in both adrenal tissue and whole blood samples collected from PCC patients. The results were strengthened by comparing recorded findings with the patients’ healthy adrenal tissue (HAT) and with whole blood samples from the healthy individuals. PCCs had significantly higher levels of Zn, Se, Na, K, and Mg and lower levels of Mn, Co, Pb, and As than that of HATs. Compared to healthy blood samples, the patients’ blood exhibited considerably higher levels of Na, K, and Ca but significantly lower levels of Mn, Cu, Zn, Se, and Mg. Females had significantly higher levels of essential Se and toxic Pb and Cd in their PCC tissue samples compared to males. PCC tissue levels of Mn and Cu were significantly elevated in smokers over levels in nonsmokers and in PCC patients with tumor sizes below 5 cm compared to PCC diameters above 5 cm. The data presented in this study provide a new insight into the pathophysiology of PCC. Thus, recorded elements should be considered as initiators/modifiers of PCC and potential inductors of malignant transformation. The findings of this research deepen scientific understanding of this rare adrenal disease, which, in turn, could highlight the pathogenesis of PCC. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Pheochromocytoma (PCC) is an unusual benign adrenal tumor with an unexamined status of the elements. This study delivers the first insight into the levels of microelements (Mn, Co, Cu, Zn, As, Se, Th), toxic elements (Cd, Pb, U), and macroelements (Na, K, Mg, Ca) in both adrenal tissue and whole blood samples collected from PCC patients. The results were strengthened by comparing recorded findings with the patients’ healthy adrenal tissue (HAT) and with whole blood samples from the healthy individuals. PCCs had significantly higher levels of Zn, Se, Na, K, and Mg and lower levels of Mn, Co, Pb, and As than that of HATs. Compared to healthy blood samples, the patients’ blood exhibited considerably higher levels of Na, K, and Ca but significantly lower levels of Mn, Cu, Zn, Se, and Mg. Females had significantly higher levels of essential Se and toxic Pb and Cd in their PCC tissue samples compared to males. PCC tissue levels of Mn and Cu were significantly elevated in smokers over levels in nonsmokers and in PCC patients with tumor sizes below 5 cm compared to PCC diameters above 5 cm. The data presented in this study provide a new insight into the pathophysiology of PCC. Thus, recorded elements should be considered as initiators/modifiers of PCC and potential inductors of malignant transformation. The findings of this research deepen scientific understanding of this rare adrenal disease, which, in turn, could highlight the pathogenesis of PCC. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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.

A growing body of evidence suggests a role of the von Hippel–Lindau (VHL) tumor suppressor gene in the progression of papillary thyroid carcinoma (PTC). Our previous study of VHL in PTCs showed that lower VHL expression was associated with aggressive tumor features, but we found no evidence for VHL downregulation through common genetic or epigenetic modifications. Several studies pointed to a role of microRNA-92a (miR-92a) in the regulation of VHL expression in different cancers. In the present study, we examined the expression levels of VHL mRNA and miR-92a in 42 pairs of PTCs and matched non-tumor thyroid tissues by means of quantitative RT-PCR. We explored the correlation between them and their association with clinicopathological parameters. The results revealed that both VHL and miR-92a were either up- or downregulated in PTCs compared to corresponding non-tumor tissues. On univariate analysis, lower VHL levels were significantly associated with extrathyroid spread (P = 0.022) and capsular invasion (P = 0.032). Multivariate analysis confirmed the association of low VHL with extrathyroid spread (OR 0.246, 95% CI 0.069–0.872, P = 0.038). Higher miR-92a among PTC tissues associated with the presence of nodal metastases (univariate analysis: P = 0.012; multivariate: OR 4.703, 95% CI 1.109–19.938, P = 0.036). A negative correlation between VHL and miR-92a was observed in a subgroup of PTCs having vascular invasion (P = 0.033, r = − 0.673). The data here reported demonstrate that the expression of both VHL and miR-92a is deregulated in PTC tissues and that in some PTCs they may have opposite roles. These roles, as well as their diagnostic and/or prognostic utility, remain to be clarified. © 2017, Springer Science+Business Media, LLC, part of Springer Nature.

A growing body of evidence suggests a role of the von Hippel–Lindau (VHL) tumor suppressor gene in the progression of papillary thyroid carcinoma (PTC). Our previous study of VHL in PTCs showed that lower VHL expression was associated with aggressive tumor features, but we found no evidence for VHL downregulation through common genetic or epigenetic modifications. Several studies pointed to a role of microRNA-92a (miR-92a) in the regulation of VHL expression in different cancers. In the present study, we examined the expression levels of VHL mRNA and miR-92a in 42 pairs of PTCs and matched non-tumor thyroid tissues by means of quantitative RT-PCR. We explored the correlation between them and their association with clinicopathological parameters. The results revealed that both VHL and miR-92a were either up- or downregulated in PTCs compared to corresponding non-tumor tissues. On univariate analysis, lower VHL levels were significantly associated with extrathyroid spread (P = 0.022) and capsular invasion (P = 0.032). Multivariate analysis confirmed the association of low VHL with extrathyroid spread (OR 0.246, 95% CI 0.069–0.872, P = 0.038). Higher miR-92a among PTC tissues associated with the presence of nodal metastases (univariate analysis: P = 0.012; multivariate: OR 4.703, 95% CI 1.109–19.938, P = 0.036). A negative correlation between VHL and miR-92a was observed in a subgroup of PTCs having vascular invasion (P = 0.033, r = − 0.673). The data here reported demonstrate that the expression of both VHL and miR-92a is deregulated in PTC tissues and that in some PTCs they may have opposite roles. These roles, as well as their diagnostic and/or prognostic utility, remain to be clarified. © 2017, Springer Science+Business Media, LLC, part of Springer Nature.

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.

Objective: To describe a rare case of acute presentation of papillary thyroid carcinoma (PTC). Clinical Presentation and Intervention: A 19-year-old male presented with an expanding cervical mass following blunt trauma. A computed tomography scan revealed a mass suspected to be hematoma that was compressing the vessels and thereby deviating the trachea. Immediate surgery was performed. Neither vascular injury nor active bleeding was seen; instead, a solid, hematoma-like tumefaction in the right thyroid lobe was revealed. A total thyroid lobectomy was performed. A histologic paraffin section confirmed a PTC that was permeated by hematoma. Conclusion: This was a unique case of an acute, life-threatening presentation of previously asymptomatic PTC in an adolescent. © 2016 S. Karger AG, Basel.

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.

Epidermal growth factor receptor (EGFR) and its downstream effector, focal adhesion kinase (FAK), have been shown to be overexpressed frequently in human malignancies and implicated in tumour aggressiveness. We aimed to investigate the relationship between EGFR and FAK expression and their possible correlation with the clinical phenotype of patients with papillary thyroid carcinoma (PTC). Expression profiles of EGFR and FAK were analysed in PTC tissue samples (n = 104) by immunohistochemistry and Western blotting. Additionally, EGFR and FAK were immunohistochemically analysed in 20 primary tumours paired with their metastatic tissue in lymph nodes. High expression of EGFR and FAK was found in 55.77% and 57.69% cases, respectively, with a strong positive association between them (P < 0.0001, Spearman's correlation coefficient = 0.844). Expression of each molecule and their coexpression correlated significantly with the presence of lymph node metastasis (LNM), degree of tumour infiltration, extrathyroid invasion and pT status of the patients. Western blot analysis confirmed that coexpression of high levels of EGFR and FAK correlated with adverse clinicopathological features. When compared to the corresponding primary tumour, increased or maintained high levels of EGFR and FAK were found in LNM, indicating their concordant expression during lymphatic spread. In conclusion, high levels of EGFR and its downstream effector, FAK, in association with lymphatic spread and tumour infiltration indicate their involvement in PTC progression and suggest that both molecules may predict its aggressive behaviour. Furthermore, FAK could be a potential target for anticancer therapy in patients with advanced thyroid cancer. © 2018 The Authors. International Journal of Experimental Pathology © 2018 International Journal of Experimental Pathology

Epidermal growth factor receptor (EGFR) and its downstream effector, focal adhesion kinase (FAK), have been shown to be overexpressed frequently in human malignancies and implicated in tumour aggressiveness. We aimed to investigate the relationship between EGFR and FAK expression and their possible correlation with the clinical phenotype of patients with papillary thyroid carcinoma (PTC). Expression profiles of EGFR and FAK were analysed in PTC tissue samples (n = 104) by immunohistochemistry and Western blotting. Additionally, EGFR and FAK were immunohistochemically analysed in 20 primary tumours paired with their metastatic tissue in lymph nodes. High expression of EGFR and FAK was found in 55.77% and 57.69% cases, respectively, with a strong positive association between them (P < 0.0001, Spearman's correlation coefficient = 0.844). Expression of each molecule and their coexpression correlated significantly with the presence of lymph node metastasis (LNM), degree of tumour infiltration, extrathyroid invasion and pT status of the patients. Western blot analysis confirmed that coexpression of high levels of EGFR and FAK correlated with adverse clinicopathological features. When compared to the corresponding primary tumour, increased or maintained high levels of EGFR and FAK were found in LNM, indicating their concordant expression during lymphatic spread. In conclusion, high levels of EGFR and its downstream effector, FAK, in association with lymphatic spread and tumour infiltration indicate their involvement in PTC progression and suggest that both molecules may predict its aggressive behaviour. Furthermore, FAK could be a potential target for anticancer therapy in patients with advanced thyroid cancer. © 2018 The Authors. International Journal of Experimental Pathology © 2018 International Journal of Experimental Pathology

Purpose: The aim of this study was to assess the clinical utility of circulating preoperative Cyfra 21.1 [soluble fragment of cytokeratin (CK) 19] and galectin-3 (gal-3) in patients with thyroid tumors, to compare their serum values with tissue expression and to analyze the prognostic significance of these markers in relation to the clinical status of postsurgical differentiated thyroid carcinoma (DTC) patients. Patients: Concentrations of Cyfra 21.1 and gal-3 were evaluated by immunoassays in sera of 9 healthy subjects, 97 preoperative patients with diverse thyroid tumors (10 FTA, 63 PTC, 11 FTC, 5 PDTC, 4 ATC, 4 LNM) and 25 postoperative DTC patients (14 remissions and 11 metastases). Results: Low Cyfra 21.1 values were found in all subgroups, but with a tendency toward higher values in poorly differentiated DTC patients. Compared to the control (0.23 ng/mL), serum levels of gal-3 were significantly elevated in patients with thyroid tumors but with overlapping between adenoma (4.16 ng/mL) and carcinoma (3.85, 4.37, 4.64, 6.07 ng/mL for PTC, PDTC, ATC and LNM, respectively). The tissue expression of CK19 and gal-3 was immunohistochemically determined on 45 matched paraffin-embedded sections. Most thyroid carcinomas showed positive CK19 (27/35) and gal-3 immunostaining (31/35), while adenomas were mostly immunonegative (8/10 and 7/10, respectively). However, there was no significant correlation between their serum and tissue levels. Clinical status of postoperative DTC patients had no influence on serum concentrations of the tested markers. Conclusions: While CK19 and gal-3 are accurate as tissue markers, their serum levels could not be used as reliable markers for identification of thyroid malignancy or in thyroid cancer follow-up. On the other hand, a tendency toward higher serum levels of Cyfra 21.1 in the small number of PDTC patients examined adds weight to previous reports postulating a role for cytokeratins in predicting a high degree of malignancy. © 2010 Springer-Verlag.

Purpose: The aim of this study was to assess the clinical utility of circulating preoperative Cyfra 21.1 [soluble fragment of cytokeratin (CK) 19] and galectin-3 (gal-3) in patients with thyroid tumors, to compare their serum values with tissue expression and to analyze the prognostic significance of these markers in relation to the clinical status of postsurgical differentiated thyroid carcinoma (DTC) patients. Patients: Concentrations of Cyfra 21.1 and gal-3 were evaluated by immunoassays in sera of 9 healthy subjects, 97 preoperative patients with diverse thyroid tumors (10 FTA, 63 PTC, 11 FTC, 5 PDTC, 4 ATC, 4 LNM) and 25 postoperative DTC patients (14 remissions and 11 metastases). Results: Low Cyfra 21.1 values were found in all subgroups, but with a tendency toward higher values in poorly differentiated DTC patients. Compared to the control (0.23 ng/mL), serum levels of gal-3 were significantly elevated in patients with thyroid tumors but with overlapping between adenoma (4.16 ng/mL) and carcinoma (3.85, 4.37, 4.64, 6.07 ng/mL for PTC, PDTC, ATC and LNM, respectively). The tissue expression of CK19 and gal-3 was immunohistochemically determined on 45 matched paraffin-embedded sections. Most thyroid carcinomas showed positive CK19 (27/35) and gal-3 immunostaining (31/35), while adenomas were mostly immunonegative (8/10 and 7/10, respectively). However, there was no significant correlation between their serum and tissue levels. Clinical status of postoperative DTC patients had no influence on serum concentrations of the tested markers. Conclusions: While CK19 and gal-3 are accurate as tissue markers, their serum levels could not be used as reliable markers for identification of thyroid malignancy or in thyroid cancer follow-up. On the other hand, a tendency toward higher serum levels of Cyfra 21.1 in the small number of PDTC patients examined adds weight to previous reports postulating a role for cytokeratins in predicting a high degree of malignancy. © 2010 Springer-Verlag.