Browsing by Author "Tatic, S. (6701763955)"

The aim of this study was to gain better insight into molecular changes which reflect disturbances in the balance between proliferation and apoptosis during progression of thyroid malignancy from papillary microcarcinoma (PMC) via clinically manifest papillary carcinoma (PTC) to anaplastic carcinoma (ATC). The apoptosis related molecules (Bcl-2, Bax) and proliferation related marker (PCNA) were analysed immunohistochemically in 120 archival cases comprising PMC (n=34), PTC (n=52) and ATC (n=34). In addition, in situ apoptotic cell death was analysed by the TUNEL method. The average Bcl-2 staining score did not differ between PMC and PTC (p>0.05), but was significantly lower in ATC (p<0.05). The Bax score was higher in PTCs and ATCs than in PMCs (p<0.05). Due to these changes, the Bcl-2/Bax ratio showed a marked decrease from PMC to ATC (p<0.05), while proliferation activity increased significantly from PTC to ATC (p<0.05). Despite high Bax expression, the rate of apoptotic cell death was low in the investigated carcinomas, especially in ATC, i.e. the increase in proliferative activity was not counterbalanced with appropriate cell death. Differences were found in the expression of apoptotic molecules (Bcl-2 and Bax), their ratio (Bcl-2/Bax) and in the rate of apoptotic cell death and proliferative activity between PMC, PTC and ATC, indicating that disturbances in the balance between apoptosis and proliferation, in favour of the latter, occur gradually during the progression of malignancy in thyroid tumours. ©2009 European Journal of Histochemistry.

The aim of this study was to gain better insight into molecular changes which reflect disturbances in the balance between proliferation and apoptosis during progression of thyroid malignancy from papillary microcarcinoma (PMC) via clinically manifest papillary carcinoma (PTC) to anaplastic carcinoma (ATC). The apoptosis related molecules (Bcl-2, Bax) and proliferation related marker (PCNA) were analysed immunohistochemically in 120 archival cases comprising PMC (n=34), PTC (n=52) and ATC (n=34). In addition, in situ apoptotic cell death was analysed by the TUNEL method. The average Bcl-2 staining score did not differ between PMC and PTC (p>0.05), but was significantly lower in ATC (p<0.05). The Bax score was higher in PTCs and ATCs than in PMCs (p<0.05). Due to these changes, the Bcl-2/Bax ratio showed a marked decrease from PMC to ATC (p<0.05), while proliferation activity increased significantly from PTC to ATC (p<0.05). Despite high Bax expression, the rate of apoptotic cell death was low in the investigated carcinomas, especially in ATC, i.e. the increase in proliferative activity was not counterbalanced with appropriate cell death. Differences were found in the expression of apoptotic molecules (Bcl-2 and Bax), their ratio (Bcl-2/Bax) and in the rate of apoptotic cell death and proliferative activity between PMC, PTC and ATC, indicating that disturbances in the balance between apoptosis and proliferation, in favour of the latter, occur gradually during the progression of malignancy in thyroid tumours. ©2009 European Journal of Histochemistry.

Aims: Galectin-3 is a beta-galactoside binding protein involved in multiple biological processes through interactions with complementary glycoconjugates. We analysed the expression and coexpression of galectin-3 and carcinoembryonic antigen (CEA), one of the putative galectin-3 ligands, in medullary thyroid carcinoma (MTC). Methods and results: An immunohistochemical study using monoclonal antibodies was performed on paraffin sections of 20 cases of sporadic MTC comprising 10 cases without and 10 cases with lymph node metastases at the time of surgery. CEA expression was found in all tumours, distributed predominantly in the cytoplasm and occasionally at the cell surface. In the majority of cases (18/20) moderate to strong intensity of staining was found in most of the cells. 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). More intense staining for galectin-3 was mainly associated with MTC cases involving lymph node metastases. Eight out of these 10 cases showed moderate to strong galectin-3 expression concomitant with CEA expression throughout the tumour tissue. Conclusions: These findings suggest that galectin-3 might play a role in the pathobiology of MTC. Simultaneous expression of galectin-3 and CEA in the same tumour cells at an advanced stage of MTC indicates the possibility of their autocrine cooperation during tumour progression.

Background and aim: To examine the relationship between galectin-3 and cell proliferation in thyroid tumor tissue. Galectin-3, a beta-galactoside binding protein, has recently been recognized as a promising molecular marker of thyroid malignancy, due to its high expression in thyroid carcinomas and absence from normal or benign thyroid tissue. However, its exact role in thyroid tumor biology is still unknown. Patients and methods: We examined the relationship between galectin-3 and cell proliferation by comparative immunostaining for galectin-3 and proliferating cell nuclear antigen (PCNA) in paraffin-embedded tissues from 126 cases of papillary thyroid carcinoma. Results: Positive cytoplasmic immunostaining for galectin-3 was found in 115 (91.3%) cases. Nuclear staining for PCNA was detectable in 93 (74.4%) cases. A low level of PCNA staining (less than 10% positive cells) was found in 36 (28.6%) cases, moderate staining for PCNA (more than 10% but less than 30% positive cells) in 35 cases (27.8%), while highly increased PCNA expression (more than 30% positive cells) was found in 32 (25.4%) cases. Moderate or strong galectin-3 expression, found in 99 cases, was associated with highly increased PCNA staining in 28.3% of them but with no detectable PCNA expression in 24.3% of them. Conclusion: These results suggest that overexpression of galectin-3 is not clearly related to proliferative activity of papillary thyroid carcinoma cells as assessed by PCNA immunostaining.

Background and aim: To examine the relationship between galectin-3 and cell proliferation in thyroid tumor tissue. Galectin-3, a beta-galactoside binding protein, has recently been recognized as a promising molecular marker of thyroid malignancy, due to its high expression in thyroid carcinomas and absence from normal or benign thyroid tissue. However, its exact role in thyroid tumor biology is still unknown. Patients and methods: We examined the relationship between galectin-3 and cell proliferation by comparative immunostaining for galectin-3 and proliferating cell nuclear antigen (PCNA) in paraffin-embedded tissues from 126 cases of papillary thyroid carcinoma. Results: Positive cytoplasmic immunostaining for galectin-3 was found in 115 (91.3%) cases. Nuclear staining for PCNA was detectable in 93 (74.4%) cases. A low level of PCNA staining (less than 10% positive cells) was found in 36 (28.6%) cases, moderate staining for PCNA (more than 10% but less than 30% positive cells) in 35 cases (27.8%), while highly increased PCNA expression (more than 30% positive cells) was found in 32 (25.4%) cases. Moderate or strong galectin-3 expression, found in 99 cases, was associated with highly increased PCNA staining in 28.3% of them but with no detectable PCNA expression in 24.3% of them. Conclusion: These results suggest that overexpression of galectin-3 is not clearly related to proliferative activity of papillary thyroid carcinoma cells as assessed by PCNA immunostaining.

Aims: Galectin-3 is a β-galactoside binding protein, recently recognized as a promising molecular marker of thyroid malignancy. As reported in several studies, galectin-3 is highly expressed in papillary thyroid carcinoma, but its expression has not been investigated in papillary microcarcinoma, which is a variant of papillary thyroid carcinoma. Methods and results: Using a monoclonal antibody to galectin-3 and the avidin-biotin-peroxidase complex (ABC) immunohistochemical technique, we analysed galectin-3 expression in 63 cases of papillary microcarcinoma. The results showed immunohistochemical reactivity for galectin-3 in 51 (80.9%) cases. Intensity of staining varied from strong or moderate to weak. Galectin-3 localization was mostly cytoplasmic, but also membranous or nuclear in some cells. Immunohistochemical expression of galectin-3 was not found in 12 (19.1%) cases. Most galectin-3 negative microcarcinomas (10/12) were of the non-classical type, i.e. without papillary architecture. Neither the frequency nor the intensity of a positive reaction was related to tumour size. Conclusions: Galectin-3 gene is expressed at the protein level in most papillary microcarcinomas, although with slightly lower frequency than that reported for clinically evident papillary thyroid carcinoma. The presence of galectin-3 in clinically silent microcarcinomas may indicate that galectin-3 is not related to growth or aggressiveness of papillary thyroid microcarcinomas but rather plays some other role in thyroid tumour biology. © 2005 Blackwell Publishing Limited.

Purpose: Since one of possible causes of resistance to antiestrogen therapy in steroid receptor positive (SR+) breast cancer (BC) patients is an alteration of PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathways, the aim of this study was to determine the PTEN protein expression in postmenopausal patients with steroid SR+ BC treated with adjuvant tamoxifen, to investigate the association of PTEN protein expression with tumor histology, size and grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) statuses and disease outcome. Methods: This was a retrospective analysis of 78 postmenopausal stage I/II SR+ BC patients treated with adjuvant tamoxifen. PTEN protein expression and ER, PR and HER2 status were determined using immunohistochemistry. Results: The distribution of PTEN protein expression according to tumor histology was as follows: PTEN+ status in 27/43 (62.8%) patients with ductal and in 26/35 (74.3%) patients with lobular carcinomas; and PTEN- status in 16/43 (37.2%) patients with ductal and in 9/35 (25.7%) patients with lobular carcinomas. Disease relapse was observed in 38/78 patients: 14/53 (26.4%) of PTEN+ BC subgroup and 24/25 (96%) of PTEN- subgroup (x2,=0.018). There were no significant associations between PTEN protein expression and tumor histology, size and grade, and ER, PR and HER2 expression. Patients with PTEN- had significantly shorter disease-free interval (DFI) and overall survival (OS) (for both, log rank test, p <0.01) compared to PTEN+ BC patients. Conclusion: Our results suggest that PTEN protein expression might be of prognostic significance in postmenopausal SR+ BC patients treated with adjuvant tamoxifen. © 2011 Zerbinis Medical Publications.

Purpose: Since one of possible causes of resistance to antiestrogen therapy in steroid receptor positive (SR+) breast cancer (BC) patients is an alteration of PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathways, the aim of this study was to determine the PTEN protein expression in postmenopausal patients with steroid SR+ BC treated with adjuvant tamoxifen, to investigate the association of PTEN protein expression with tumor histology, size and grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) statuses and disease outcome. Methods: This was a retrospective analysis of 78 postmenopausal stage I/II SR+ BC patients treated with adjuvant tamoxifen. PTEN protein expression and ER, PR and HER2 status were determined using immunohistochemistry. Results: The distribution of PTEN protein expression according to tumor histology was as follows: PTEN+ status in 27/43 (62.8%) patients with ductal and in 26/35 (74.3%) patients with lobular carcinomas; and PTEN- status in 16/43 (37.2%) patients with ductal and in 9/35 (25.7%) patients with lobular carcinomas. Disease relapse was observed in 38/78 patients: 14/53 (26.4%) of PTEN+ BC subgroup and 24/25 (96%) of PTEN- subgroup (x2,=0.018). There were no significant associations between PTEN protein expression and tumor histology, size and grade, and ER, PR and HER2 expression. Patients with PTEN- had significantly shorter disease-free interval (DFI) and overall survival (OS) (for both, log rank test, p <0.01) compared to PTEN+ BC patients. Conclusion: Our results suggest that PTEN protein expression might be of prognostic significance in postmenopausal SR+ BC patients treated with adjuvant tamoxifen. © 2011 Zerbinis Medical Publications.

Aims: The objective of the study was to report a series of patients with Hürthle cell tumours. Methods: We reviewed medical records of single institution from January 1982 to December 2002, including follow-up information. Results: We identified 199 patients with Hürthle cell tumours (HCT), 88 patients with Hürthle cell carcinoma (HCC) and 111 patients with Hürthle cell adenoma (HCA). The HCC group had significantly longer duration of the disease and larger tumours (4.8 vs 3.8 cm) compared with HCA group. Gender appeared to play significant role in patients with HCT (women outnumbered man by 7:1; p<0.01). Surgical management for 80% of patients with HCA consisted of hemithyroidectomy and total thyroidectomy in 87% patients in the HCC group. Temporary laryngeal nerve palsy and temporary hypoparathyroidismus were not seen in HCA group, in HCC group were confirmed in 2.27 and 3.41%, respectively. Four patients with HCC relapsed and two died of HCC. Conclusions: HCC has outlook for favorable outcome when treated radically with total thyroidectomy. © 2006 Elsevier Ltd. All rights reserved.

Aim: Expression of thyroid peroxidase (TPO) in the thyroid gland tissue is well known as a sensitive marker of the thyroid malignancy. We have evaluated immunohistochemical assay of TPO for distinguishing follicular thyroid carcinoma from follicular adenoma. Materials and Methods: Sections of formalin-fixed tissues obtained from 92 patients with thyroid tumors (52 follicular carcinomas and 40 follicular adenomas including the Hürthle cell type) were analyzed using a monoclonal antibody (TPO mAb 47) and the avidin-biotin peroxidase complex immunohistochemical technique. Lesions with staining of more than 80% of the follicular cells/specimen were considered benign, while less than 80% were considered malignant. Results: TPO immunostaining correlated with the histopathological diagnosis in 24/40 cases of follicular adenomas and 41/52 cases of follicular carcinomas, giving a specificity of 60% and a sensitivity of 79%. Conclusion: These results suggest that immunohistochemical assay of TPO expression has limited value for the differential diagnosis of follicular thyroid carcinoma from thyroid follicular adenoma.

Aim: Expression of thyroid peroxidase (TPO) in the thyroid gland tissue is well known as a sensitive marker of the thyroid malignancy. We have evaluated immunohistochemical assay of TPO for distinguishing follicular thyroid carcinoma from follicular adenoma. Materials and Methods: Sections of formalin-fixed tissues obtained from 92 patients with thyroid tumors (52 follicular carcinomas and 40 follicular adenomas including the Hürthle cell type) were analyzed using a monoclonal antibody (TPO mAb 47) and the avidin-biotin peroxidase complex immunohistochemical technique. Lesions with staining of more than 80% of the follicular cells/specimen were considered benign, while less than 80% were considered malignant. Results: TPO immunostaining correlated with the histopathological diagnosis in 24/40 cases of follicular adenomas and 41/52 cases of follicular carcinomas, giving a specificity of 60% and a sensitivity of 79%. Conclusion: These results suggest that immunohistochemical assay of TPO expression has limited value for the differential diagnosis of follicular thyroid carcinoma from thyroid follicular adenoma.

Purposes of the study: In contrast to familial medullary carcinoma, familial nonmedullary thyroid carcinoma (FNMTC) is less frequent and has been less investigated. The aim of this study was to determine the frequency of FNMTC and analyse the main demographic and clinical characteristics of the patients. Material and methods: Data on 1411 patients surgically treated for nonmedullary thyroid carcinoma, in the Center for Endocrine Surgery in Belgrade, from 1995 to 2006 were analysed. The possible presence of malignant tumours of the thyroid gland was investigated in their closest relatives in order to identify cases of FNMTC. Only data on first-degree relatives (parents and children) and second-degree relatives (grandparents, grandchildren and siblings) were taken into account in the analysis. Results: Thirteen patients (11 females and 2 males) (0.92% of those with nonmedullary carcinoma of the thyroid gland) had a familial form of the disease. In five families two members had a tumour, and in one family three members. In five out of six families it was a papillary carcinoma and in one family a follicular carcinoma. Patient age varied from 20 to 79 years, with a mean age of 40 years. The tumour size ranged from 5 to 60 mm (mean 25 mm). In two of the thirteen cases the tumour penetrated the capsule of the thyroid gland. In four cases the tumour was multicentric and bilateral, and in a further two metastases were present in regional lymph nodes. During the follow-up period, which lasted from 2 to 12 years (mean 8.5 years), two relapses were detected. Conclusion: Familial nonmedullary carcinoma of the thyroid gland occurs very rarely.