Immunohistochemical detection of epithelialmesenchymal transition associated with stemness phenotype in anaplastic thyroid carcinoma

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.

Keywords: Anaplastic thyroid carcinoma; cancer stem cell; epithelial-mesenchymal transition; follicular thyroid carcinoma; immunohistochemistry; papillary thyroid carcinoma.

Figure 1

Immunohistochemical staining of nestin in : A. anaplastic thyroid carcinoma (Original magnification × 400); B. adjacent non-neoplastic thyroid tissue (Original magnification × 400); C. papillary thyroid carcinoma component (lower portion)contiguous anaplastic thyroid carcinoma (upper portion) (Original magnification × 200); and D. follicular carcinoma (Original magnification × 400).

Figure 2

Immunohistochemical staining ofE-cadherin in: A. anaplastic thyroid carcinoma (original magnification × 400); B. adjacent non-neoplastic thyroid tissue (original magnification × 400); C. papillary thyroid carcinoma component (original magnification × 400) and D. follicular carcinoma component (original magnification × 400).