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.

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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: 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. V C 2015 American Cancer Society.

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.

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.

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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.