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Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas.

Cunha LL, Morari EC, Nonogaki S, Soares FA, Vassallo J, Ward LS - Clinics (Sao Paulo) (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: University of Campinas, Faculty of Medical Sciences, Laboratory of Cancer Molecular Genetics, SP, Brazil.

ABSTRACT

Objectives: 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.

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Related in: MedlinePlus

Cytoplasmic FoxP3 immunostaining in different thyroid tissues. This boxplot of the immunohistochemical quantification data provides evidence of progressive FoxP3 staining in different stages of tumor evolution. Computer-generated numerical values that represent the intensity and extent of the brown (FoxP3) staining are plotted on the y-axis. Abbreviations: NT = normal thyroid; G = goiter; FA = follicular adenoma; FVPTC = follicular variant of papillary thyroid carcinoma; CPTC = classic papillary thyroid carcinoma; FC = follicular carcinoma.
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f2-cln_67p483: Cytoplasmic FoxP3 immunostaining in different thyroid tissues. This boxplot of the immunohistochemical quantification data provides evidence of progressive FoxP3 staining in different stages of tumor evolution. Computer-generated numerical values that represent the intensity and extent of the brown (FoxP3) staining are plotted on the y-axis. Abbreviations: NT = normal thyroid; G = goiter; FA = follicular adenoma; FVPTC = follicular variant of papillary thyroid carcinoma; CPTC = classic papillary thyroid carcinoma; FC = follicular carcinoma.

Mentions: A close relationship was found between the results of the semiquantitative and quantitative analyses of both the cytoplasmic (p<0.0001) and nuclear FoxP3 staining (p<0.0001); however, the numerical values were not distributed according to a Gaussian curve. We found no significant differences between the cytoplasmic FoxP3 staining levels of the female (52.3±37.4) and male (41.6±40.5, p = 0.0641) differentiated thyroid carcinoma patients. The cytoplasmic FoxP3 levels were inversely correlated with the patient's age at the of the differentiated thyroid carcinoma diagnosis (Spearman r = -0.2913, p = 0.0001). The Kruskal-Wallis test showed distinct patterns of FoxP3 expression among the different types of lesions (p<0.0001), with the malignant lesions staining more intensely (48.1±36.2) than the benign ones (31.9±25.8, p = 0.0005) (Figure 2). The normal thyroid tissues exhibited the lowest cytoplasmic staining (10.9±4.8). The classic papillary thyroid carcinomas received higher staining scores (55.8±38.6) than goiters (22.8±19.6, p<0.0001) and follicular carcinomas (32.5±18.9, p = 0.0143). A multivariate logistic regression model indicated that cytoplasmic FoxP3 expression may be an independent risk factor for malignancy in the diagnosis of thyroid nodules, albeit with a relatively low sensitivity and specificity (Table 1). The differentiated thyroid carcinoma tumors with concurrent chronic lymphocytic thyroiditis exhibited higher cytoplasmic FoxP3 expression (67.6±42.8) when compared with those with no concurrent chronic lymphocytic thyroiditis (46.1 ± 35.6, p = 0.0043).


Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas.

Cunha LL, Morari EC, Nonogaki S, Soares FA, Vassallo J, Ward LS - Clinics (Sao Paulo) (2012)

Cytoplasmic FoxP3 immunostaining in different thyroid tissues. This boxplot of the immunohistochemical quantification data provides evidence of progressive FoxP3 staining in different stages of tumor evolution. Computer-generated numerical values that represent the intensity and extent of the brown (FoxP3) staining are plotted on the y-axis. Abbreviations: NT = normal thyroid; G = goiter; FA = follicular adenoma; FVPTC = follicular variant of papillary thyroid carcinoma; CPTC = classic papillary thyroid carcinoma; FC = follicular carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351250&req=5

f2-cln_67p483: Cytoplasmic FoxP3 immunostaining in different thyroid tissues. This boxplot of the immunohistochemical quantification data provides evidence of progressive FoxP3 staining in different stages of tumor evolution. Computer-generated numerical values that represent the intensity and extent of the brown (FoxP3) staining are plotted on the y-axis. Abbreviations: NT = normal thyroid; G = goiter; FA = follicular adenoma; FVPTC = follicular variant of papillary thyroid carcinoma; CPTC = classic papillary thyroid carcinoma; FC = follicular carcinoma.
Mentions: A close relationship was found between the results of the semiquantitative and quantitative analyses of both the cytoplasmic (p<0.0001) and nuclear FoxP3 staining (p<0.0001); however, the numerical values were not distributed according to a Gaussian curve. We found no significant differences between the cytoplasmic FoxP3 staining levels of the female (52.3±37.4) and male (41.6±40.5, p = 0.0641) differentiated thyroid carcinoma patients. The cytoplasmic FoxP3 levels were inversely correlated with the patient's age at the of the differentiated thyroid carcinoma diagnosis (Spearman r = -0.2913, p = 0.0001). The Kruskal-Wallis test showed distinct patterns of FoxP3 expression among the different types of lesions (p<0.0001), with the malignant lesions staining more intensely (48.1±36.2) than the benign ones (31.9±25.8, p = 0.0005) (Figure 2). The normal thyroid tissues exhibited the lowest cytoplasmic staining (10.9±4.8). The classic papillary thyroid carcinomas received higher staining scores (55.8±38.6) than goiters (22.8±19.6, p<0.0001) and follicular carcinomas (32.5±18.9, p = 0.0143). A multivariate logistic regression model indicated that cytoplasmic FoxP3 expression may be an independent risk factor for malignancy in the diagnosis of thyroid nodules, albeit with a relatively low sensitivity and specificity (Table 1). The differentiated thyroid carcinoma tumors with concurrent chronic lymphocytic thyroiditis exhibited higher cytoplasmic FoxP3 expression (67.6±42.8) when compared with those with no concurrent chronic lymphocytic thyroiditis (46.1 ± 35.6, p = 0.0043).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: University of Campinas, Faculty of Medical Sciences, Laboratory of Cancer Molecular Genetics, SP, Brazil.

ABSTRACT

Objectives: 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.

Show MeSH
Related in: MedlinePlus