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Expression of cancer stem cell markers is more frequent in anaplastic thyroid carcinoma compared to papillary thyroid carcinoma and is related to adverse clinical outcome
  1. Ji Yun Yun1,
  2. Young A Kim2,
  3. Ji-Young Choe1,
  4. Hyesook Min1,
  5. Kyu Sang Lee1,
  6. Youngho Jung3,
  7. Sohee Oh4,
  8. Ji Eun Kim2
  1. 1Department of Pathology, Seoul National University Hospital, Seoul, Korea
  2. 2Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea
  3. 3Department of Otolaryngology, Seoul National University Boramae Hospital, Seoul, Korea
  4. 4Department of Biostatistics, Seoul National University Boramae Hospital, Seoul, Korea
  1. Correspondence to Dr Ji Eun Kim, Department of Pathology, Seoul National University Boramae Hospital, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 156-707, Korea; npol181{at}snu.ac.kr

Abstract

Background Thyroid cancer is one of the most commonly detected cancers worldwide, and papillary thyroidal carcinoma (PTC) accounts for the majority of thyroid cancers. In contrast to the indolent nature of PTC, anaplastic thyroid carcinoma (ATC) shows an extremely poor prognosis and has not responded to any therapeutic modalities. Many researchers postulate that the dedifferentiation of thyroid follicular cells into primitive cells might be related to the pathogenesis of ATC because several cases of ATC have revealed pre-existing PTC lesions. Additionally, the cancer stem cell (CSC) theory has been widely accepted in the pathogenesis of ATC.

Objective To explore the expression of various CSC markers in thyroid carcinoma tissues and analyse their clinical significance.

Methods 133 patients with PTC and 25 patients with ATC were enrolled. Immunohistochemistry for aldehyde dehydrogenase 1 (ALDH1), CD133, CXCR4, ATP-binding cassette (ABC)G2, multidrug resistance associated protein-1 (MRP1), lung resistance protein-1 (LRP), P-glycoprotein 1 (P-Gp1), SOX2, SOX9 and Oct4 was performed using tissue microarray.

Results CSC marker expression was significantly high in ATC, particularly chemoresistance markers such as ABCG2, MRP1, LRP and CXCR4. In PTC, ABCG2 was highly positive in more advanced pathological stages and was associated with lymph node involvement, with borderline significance. In ATC, high expression of CXCR4 correlated with distant metastasis, and LRP showed a tendency to correlate with lymph node metastasis. High expression of CSC markers was related to shorter overall survival in patients with ATC.

Conclusions These results provide strong evidence that CSCs are related to the pathogenesis of ATC and can explain the frequent treatment failure and aggressiveness of ATC.

  • Thyroid Cancer
  • Carcinoma
  • Immunohistochemistry

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