Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas.
OBJECTIVE
Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3(+) lymphocyte infiltration in differentiated thyroid carcinoma cells.


METHODS
We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues.


RESULTS
We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3(+) lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis.


CONCLUSIONS
We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness.
University of Campinas, Faculty of Medical Sciences, Laboratory of Cancer Molecular Genetics, SP, Brazil.
Lucas Leite
LL
Cunha
Elaine Cristina
EC
Morari
Suely
S
Nonogaki
Fernando Augusto
FA
Soares
José
J
Vassallo
Laura Sterian
LS
Ward
D018263:Adenocarcinoma, Follicular; D000328:Adult; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D002291:Carcinoma, Papillary; D002454:Cell Differentiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry*; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000473:pathology; D046888:Tissue Array Analysis / Q000379:methods
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins