Dubravka Cvejić

Galectin-3 and carcinoembryonic antigen expression in medullary thyroid carcinoma: possible relation to tumour progression

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).

Combined immunohistochemistry for thyroid peroxidase, galectin-3, CK19 and HBME-1 in differential diagnosis of thyroid tumors

Paunovic I, Isic T, Havelka M, Tatic S, Cvejic D, Savin S. Combined immunohistochemistry for thyroid peroxidase, galectin‐3, CK19 and HBME‐1 in differential diagnosis of thyroid tumors. APMIS 2012; 120: 368–79.

Thyroid peroxidase and galectin-3 immunostaining in differentiated thyroid carcinoma with clinicopathologic correlation

Thyroperoxidase and galectin-3 have been reported as useful immunohistochemical markers of thyroid malignancy. In this study, we evaluated the relationship between immunohistochemical staining results for these markers and clinicopathologic features of patients with differentiated thyroid cancer. A total of 193 archival thyroid samples including 28 follicular adenomas, 18 follicular carcinomas, and 147 papillary carcinomas with 114 adjacent thyroid tissues were analyzed by immunohistochemistry. Thyroperoxidase was underexpressed (<50% stained thyrocytes), and galectin-3 was expressed (>5% stained thyrocytes) in most carcinomas. The sensitivity for diagnosis of differentiated thyroid carcinoma was 86.1% for thyroperoxidase and 82.4% for galectin-3, whereas the combination of both markers increased the sensitivity up to 94.5%. Thus, the combination of thyroperoxidase and galectin-3 immunohistochemistry may help to ascertain the malignant nature of the lesion. Furthermore, tumor size, nodal involvement, extrathyroidal invasion, and high tumor-node-metastasis stage in patients with papillary carcinoma were related to thyroperoxidase absence and high galectin-3 expression in most cases (P < .05). In patients with follicular carcinoma, the extent of invasiveness was associated with galectin-3 positivity. Thus, expression of these markers is related to more or less aggressive biological behavior of differentiated thyroid carcinomas. Although thyroperoxidase presence may indicate favorable prognosis of papillary cancer, expression of galectin-3 illustrates the potential importance of this protein in the pathogenesis and/or progression of differentiated thyroid carcinomas.

Galectin-3 expression in papillary thyroid carcinoma: relation to histomorphologic growth pattern, lymph node metastasis, extrathyroid invasion, and tumor size.

Galectin‐3 has been recently recognized as a promising presurgical marker of thyroid malignancy.

Comparison of the influence of thyroglobulin antibodies on serum thyroglobulin values from two different immunoassays in post surgical differentiated thyroid carcinoma patients

Measurement of serum thyroglobulin (Tg) is a highly specific test in the management of patients with differentiated thyroid cancer (DTC) after surgical treatment. The aim of our study was to evaluate and compare Tg levels in these patients found by radioimmunoassay (RIA) and immunoradiometric assay (IRMA) and to assess the influence of Tg antibodies (TgAbs) on the values obtained for Tg concentration. Both Tg and TgAb were determined postoperatively in the serum of 71 DTC patients using RIA Tg‐PEG (INEP) and Tg IRMA (CIS) for Tg, together with TgAb (CIS) for circulating endogenous anti‐TgAbs. The obtained concentrations were evaluated statistically. We found a significant difference of Tg concentrations between paired samples from the IRMA and RIA, although the intermethod comparison yielded satisfactory concordance of the twoassays (Spearman correlation coefficient −0.792). Positive TgAb was found in 28.2% of the serum samples analyzed. Spearman rank correlation analysis revealed a significant negative relationship between serum TgAb and Tg level measured by IRMA (P=0.02), but not by RIA (P=0.417). On the other hand, our clinical data revealed that 1/18 and 3/18 patients with proven lymph node metastasis had Tg values below the detection limit by RIA and IRMA assay, respectively. Their sera were TgAb positive. We concluded that RIA was less prone to influence of TgAb than IRMA. As the presence of TgAbs may interfere in Tg measurement irrespective of the method selected for determination, this should be considered during the clinical management of these patients. J. Clin. Lab. Anal. 23:341–346, 2009.

Galectin‐3 expression in papillary microcarcinoma of the thyroid

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.

Apoptosis and proliferation related molecules (Bcl-2, Bax, p53, PCNA) in papillary microcarcinoma versus papillary carcinoma of the thyroid.

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.

Thyroid peroxidase immunohistochemistry in differential diagnosis of thyroid tumors.

Thyroperoxidase (TPO) is a thyroid-specific enzyme expressed by differentiated thyroid cells. Initial immunohistochemical studies claimed that TPO expression, detected by the monoclonal antibody mAb 47, may be a potentially important diagnostic tool in differentiating malignant from benign lesions. However, some recent studies have failed to reproduce the earlier results, suggesting the limitations for TPO immunohistochemistry. To assess these observations we have evaluated the immunohistochemical expression of TPO in thyroid tissue from 215 patients. The studied material included 87 nonmalignant thyroid lesions and 128 thyroid carcinomas. TPO expression was investigated using newly available mAb 47 and staining of less than 80% of the follicular cells/specimen as the threshold indicating a malignant lesion. We found that TPO had a sensitivity of 89.9% for cancer and a specificity of 64.4% for nonmalignant lesions, showing that it does not give a sufficient degree of diagnostic certainty that the lesion is benign. In addition, the variability in the degree of TPO expression found within and between follicular carcinomas, and the significant number of benign adenomas having similar immunostaining patterns, assured us that TPO immunostaining is not sufficiently discriminatory in the differential diagnosis of thyroid cancer versus benign lesions.

Defining the value of CD56, CK19, Galectin 3 and HBME-1 in diagnosis of follicular cell derived lesions of thyroid with systematic review of literature.

BackgroundNodular follicular lesions of thyroid gland comprise benign and malignant neoplasms, as well as some forms of hyperplasia. “Follicular” refers to origin of cells and in the same time to growth pattern - building follicles. Nodular follicular thyroid lesions have in common many morphological features, therefore attempts were made to define additional criteria for distinction between follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma. Increasing number of immunohistochemical markers is in the continual process of evaluation.MethodsTissue microarrays incorporating, total 201 cases, out of which 122 malignant and 79 benign follicular lesions, including neoplastic and non-neoplastic, were constructed and immunostained with antibodies to CD56, CK19, Galectin-3, HBME-1. Tissue cores were exclusively being acquired from tumour/lesion on interface with normal thyroid tissue. A systematic review of literature was done for period from the year 2001 to present time.ResultsAll analysed markers may make a difference between benign lesions/tumours from differentiated thyroid carcinomas (p = <0.01, for all markers). Expression of all markers is significantly higher in papillary carcinoma than in follicular adenoma (p < 0.01). Statistically significant difference in expression of Galectin-3 and CD56 between follicular carcinoma and follicular adenoma was registered (p = 0.043; p = 0.028, respectively). The only marker which expression showed statistically significant difference between adenoma and carcinoma of Hurthle cells was Galectin 3 (p = 0.041). CK19 and HBME-1 were significantly expressed more in papillary carcinoma as compared to follicular carcinoma.ConclusionGalectin 3 is most sensitive marker for malignancy, while loss of expression of CD56 is very specific for malignancy. Expected co-expression for combination of markers in diagnosis of follicular lesions decreases sensitivity and increases specificity for malignancy.

Enhanced acid protease activity of lysosomes from papillary thyroid carcinoma

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.