title: 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.
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.
authors.affiliation: Department of Pathology, Seoul National University Hospital, , Seoul, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Yun
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choe
authors.forename: Hyesook
authors.initials: H
authors.lastname: Min
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Lee
authors.forename: Youngho
authors.initials: Y
authors.lastname: Jung
authors.forename: Sohee
authors.initials: S
authors.lastname: Oh
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult
keywords: Carcinoma; Immunohistochemistry; Thyroid Cancer