Coexistent Anaplastic and Differentiated Thyroid Carcinoma.

Central Laboratory for Clinical Investigation, Miyazaki University Hospital, Miyazaki, Japan.
American Journal of Clinical Pathology (Impact Factor: 2.88). 04/2006; 125(3):399-406. DOI: 10.1309/LF3Q-1NQK-MT2N-9KNV
Source: PubMed

ABSTRACT 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.

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    European Journal of Nuclear Medicine 10/2012; 40(1). · 4.53 Impact Factor
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    ABSTRACT: Accumulating evidence supports the notion that thyroid cancer is initiated by tumor-initiating cells (TICs) (commonly known as cancer stem cells), which are thought to play a crucial role in malignant progression, therapeutic resistance and recurrence. Thyroid TICs have been isolated and identified using specific biomarkers (such as CD133), the side population, sphere formation and aldehyde dehydrogenase activity assays. Although their characteristics remain largely unknown, TICs provide an attractive cellular mechanism to explain therapeutic refractoriness. Efforts are currently being directed toward the identification of therapeutic strategies that could target these cells. The present review discusses the cellular origins of TICs and the main approaches used to isolate and identify thyroid TICs, with a focus on the remaining challenges and opportunities for anticancer therapy.
    Oncology Reports 01/2014; · 2.19 Impact Factor
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    ABSTRACT: Background: Epithelial-to-mesenchymal transition (EMT) has been thought to play a critical role in invasion and metastasis of cancer and to be associated with cancer stem cell (CSC) properties. It is not clear if there is a link between EMT and CSCs in thyroid cancers. We therefore investigated CSC properties of thyroid cancers that underwent EMT. Method: To induce EMT (spindle-like cell morphology, loss and acquisition of expression of an epithelial marker E-cadherin and a mesenchymal marker vimentin, respectively) in an epithelial type thyroid cancer cell line ACT-1, we used transforming growth factor-beta (TGF-beta), BRAFV600E and/or Snail homolog 1 (SNAI1, also known as SNAIL) . CSC properties were analyzed with assays for cell proliferation, chemosensitivity, in vitro and in vivo tumor formation ability, cell surface antigens and intracellular aldehyde dehydrogenase (ALDH; a known CSC marker) activities. Results: EMT was induced most efficiently by SNAIL (ACT-SNAIL cells), whereas TGF-beta and BRAFV600E were less efficient. ACT-SNAIL cells showed slightly but significantly enhanced tumor formation ability in in vitro sphere assay (~3 fold) but not in vivo subcutaneous tumor growth assay, and showed comparable chemosensitivity, as compared to the parental ACT-1 cells. However, of interest, although in vitro sphere formation ability of ALDH+ cells was almost unchanged after SNAIL induction, SNAIL overexpression induced much higher (~14 fold) spheres in ALDH- cells. Thus, ALDH was no longer a CSC marker in ACT-SNAIL cells. Conclusions: All these data indicate that EMT confers CSC properties in ALDH- cells and appears to influence the ability of ALDH to enrich CSCs.
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