The aim of the present study was to clarify the underlying molecules that might contribute to the highly aggressive behavior of anaplastic thyroid carcinoma. We selected 5 cases of anaplastic thyroid carcinoma that had a differentiated area to determine differences in the molecules of undifferentiated and differentiated cancer cells. We immunohistochemically examined the localization of nuclear antigen (Ki-67), proliferating cell nuclear antigen (PCNA), p53, apoptotic protease-activating factor-1 (Apaf-1), CD26, galectin-3, E-cadherin, and CD147. We found an increased Ki-67, PCNA, and p53 labeling indices; decreased levels of Apaf-1, CD26, galectin-3, and E-cadherin; and overexpression of CD147 in the undifferentiated area compared with the differentiated area. These findings indicate high proliferative properties, suppression of apoptosis, disruption of cell-cell interaction, and induction of matrix metalloproteinases in the undifferentiated areas. Thus the molecules examined might be useful for evaluating the aggressive nature of this tumor and the prognosis.
[Show abstract][Hide abstract] ABSTRACT: Selection of novel molecular markers is an important goal of cancer genomics studies. The aim of our analysis was to apply the multivariate bioinformatical tools to rank the genes - potential markers of papillary thyroid cancer (PTC) according to their diagnostic usefulness. We also assessed the accuracy of benign/malignant classification, based on gene expression profiling, for PTC. We analyzed a 180-array dataset (90 HG-U95A and 90 HG-U133A oligonucleotide arrays), which included a collection of 57 PTCs, 61 benign thyroid tumors, and 62 apparently normal tissues. Gene selection was carried out by the support vector machines method with bootstrapping, which allowed us 1) ranking the genes that were most important for classification quality and appeared most frequently in the classifiers (bootstrap-based feature ranking, BBFR); 2) ranking the samples, and thus detecting cases that were most difficult to classify (bootstrap-based outlier detection). The accuracy of PTC diagnosis was 98.5% for a 20-gene classifier, its 95% confidence interval (CI) was 95.9-100%, with the lower limit of CI exceeding 95% already for five genes. Only 5 of 180 samples (2.8%) were misclassified in more than 10% of bootstrap iterations. We specified 43 genes which are most suitable as molecular markers of PTC, among them some well-known PTC markers (MET, fibronectin 1, dipeptidylpeptidase 4, or adenosine A1 receptor) and potential new ones (UDP-galactose-4-epimerase, cadherin 16, gap junction protein 3, sushi, nidogen, and EGF-like domains 1, inhibitor of DNA binding 3, RUNX1, leiomodin 1, F-box protein 9, and tripartite motif-containing 58). The highest ranking gene, metallophosphoesterase domain-containing protein 2, achieved 96.7% of the maximum BBFR score.
Endocrine Related Cancer 10/2007; 14(3):809-26. DOI:10.1677/ERC-06-0048 · 4.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Galectin-3 plays important roles in cell adhesion, cell proliferation, apoptosis, neoplastic transformation, and metastasis. Galectin-3 expression has been evaluated in various malignant neoplasms to determine its effectiveness in differential diagnosis from benign lesions and its effects on carcinogenesis. There are few and somewhat controversial results regarding its changes through cancer progression in thyroid malignancies. We studied the presence of galectin-3 expression immunohistochemically and its relation with tumor invasiveness and lymph node metastasis in 89 cases of papillary carcinoma of the thyroid. Galectin overexpression was less frequent in cases with lymph node metastases compared with cases without lymph node metastasis (P = 0.001). Metastatic foci in lymph nodes showed a lower degree of galectin-3 overexpression than their primary lesions (P = 0.001). Degree of galectin-3 overexpression was also lower in larger tumors (P = 0.009). Additionally, a decreased level of galectin-3 overexpression was observed at the invasive edges of the tumors (P = 0.001). Galectin-3 overexpression is more profound in early stages of papillary carcinoma, and its expression intensity decreases during tumor progression. This finding is consistent with roles for galectin-3 in cell adhesion to other tumor cells and the matrix.
[Show abstract][Hide abstract] ABSTRACT: Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm resistant to radiation and chemotherapy. Epithelial-mesenchymal transition (EMT) generating cells with stem cell characteristics have been reported to be associated with chemoradioresistance in cultured cells. However, EMT and stem cell properties in ATC have not been fully investigated. In this study, we retrieved 2 thyroidectomy specimens of ATC with coexisting well differentiated thyroid carcinomas (DTCs) including one papillary carcinoma (PTC) and one follicular carcinoma (FTC). We used im-munohistochemistry to examine the expression of stem cell markers (nestin, CD133 and CD44) and a marker for EMT (E-cadherin). Intense expressions of nestin, CD133 and CD44, and no expression of E-cadherin were observed in both ATCs. In contrast, the PTC and FTC, and non-neoplastic thyroid tissue in both cases were negative for nestin and positive for E-cadherin. The expressions of CD133 and CD44 were variable in the PTC, FTC, and non-neoplastic thyroid tissue and were at a lower level of expression of these markers in the overall pattern. The results confirmed EMT, demonstrated the stem cell phenotype in ATC, and revealed the difference in expression of these markers between ATC and DTCs/non-neoplastic thyroid tissue. Nestin may be the most specific marker for stemness in ATC by immuno-histochemial staining. The results warrant future studies on a large series of cases in order to gain the understanding of the tumor biology and to provide molecular basis for restoring the sensitivities to clinical therapies.
International journal of clinical and experimental pathology 01/2010; 3(8):755-62. · 1.89 Impact Factor
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