title: Patterns of FOXE1 expression in papillary thyroid carcinoma by immunohistochemistry.
abstract: BACKGROUND
  FOXE1, a thyroid-specific transcription factor also known as TTF-2, was recently identified as a major genetic risk factor for papillary thyroid carcinoma (PTC). Its role in thyroid carcinogenesis, however, remains unknown. The purpose of the present study was to assess the relationship between the FOXE1 immunohistochemical features and the clinical and genetic characteristics of PTC.
  
  
  METHODS
  Immunohistochemical staining of FOXE1 was performed in 48 PTC cases. Two single nucleotide polymorphisms immediately inside (rs1867277) or in the vicinity (rs965513) of the FOXE1 gene were genotyped by direct sequencing. Histopathological, clinical, and genetic data were included in statistical analyses.
  
  
  RESULTS
  FOXE1 exhibited cytoplasmic overexpression in tumor tissue compared to the normal counterpart (p<0.001). Both cancer and normal thyroid cells demonstrated the highest FOXE1 scores in the areas closest to the tumor border (<300 μm) compared with more distant areas (p<0.001). No differences in FOXE1 staining distributions were found between microcarcinomas and PTC of larger size, between different histopathological variants of PTC, and encapsulated and nonencapsulated tumors. Multivariate regression analysis revealed that nuclear FOXE1 expression in neoplastic cells in the vicinity of the tumor border independently associated with the genotype at rs1867277 (the dominant model of inheritance, p=0.037) and tumor multifocality (p=0.032), and with marginal significance with capsular invasion (p=0.051).
  
  
  CONCLUSIONS
  FOXE1 overexpression and translocation to the cytoplasm are phenotypic hallmarks of tumor cells suggesting that FOXE1 is involved in the pathogenesis of PTC. Nuclear FOXE1 expression in tumor cells in the vicinity of the PTC border is associated with the presence of a risk allele of rs1867277 (c.-238G>A) in the 5' untranslated region of the FOXE1 gene, as well as with pathological characteristics of PTC, suggesting possible FOXE1 involvement in the facilitation of tumor development beginning at an early stage.
authors: Department of Radiation Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Andrey
authors: A
authors: Bychkov
authors: Vladimir
authors: V
authors: Saenko
authors: Masahiro
authors: M
authors: Nakashima
authors: Norisato
authors: N
authors: Mitsutake
authors: Tatiana
authors: T
authors: Rogounovitch
authors: Alyaksandr
authors: A
authors: Nikitski
authors: Florence
authors: F
authors: Orim
authors: Shunichi
authors: S
authors: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors