title: FoxP3 expression in papillary thyroid carcinoma: a possible resistance biomarker to iodine 131 treatment.
abstract: BACKGROUND
  The forkhead transcription factor FoxP3 plays an important role in regulatory T cell (Treg) functions. Tregs are critical in maintaining immunologic tolerance. It has been shown that vaccination against FoxP3-expressing cells is associated with enhancement of tumor immunity. Tregs appear to be increased in blood and in the tumor microenvironment of patients with different cancer types. Tumor cells themselves can express FoxP3. The present study investigates the possible role of FoxP3 expression in a series of human papillary thyroid cancers with a mean follow-up time of 15 years.
  
  
  METHODS
  One hundred five cases of papillary thyroid carcinoma (PTC) were investigated, and FoxP3 expression was evaluated in both tumor cells and tumor-associated infiltrates. For all patients, clinical/pathologic features were considered and the results analyzed by statistical tests.
  
  
  RESULTS
  Of the 105 PTC cases, 45 (43%) scored FoxP3-positive and 60 (57%) were negative. FoxP3 staining was localized predominantly in the cytoplasm of tumor cells. In some cases, both nuclear and cytoplasmic staining was seen in infiltrating cells. FoxP3 expression in tumor cells was correlated with the presence of extrathyroid invasion (p=0.04) and distant metastasis (p=0.04), but not with overall survival. Interestingly, FoxP3 expression in neoplastic cells was significantly associated with a resistance phenotype to radioiodine treatment (p=0.041).
  
  
  CONCLUSIONS
  The data show an association of FoxP3 expression with features of PTC that seem to have a specific impact on radioiodine sensitivity.
authors.affiliation: 1 Department of Laboratory Medicine, Azienda Ospedaliero-Universitaria Pisana , Pisa, Italy .
authors.forename: Clara
authors.initials: C
authors.lastname: Ugolini
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
authors.forename: Agnese
authors.initials: A
authors.lastname: Proietti
authors.forename: Serena
authors.initials: S
authors.lastname: Pelliccioni
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lupi
authors.forename: Nicla
authors.initials: N
authors.lastname: Borrelli
authors.forename: David
authors.initials: D
authors.lastname: Viola
authors.forename: Pietro
authors.initials: P
authors.lastname: Leocata
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Toniolo
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000276:immunology / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000276:immunology / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000276:immunology / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007457:Iodine Radioisotopes