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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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Different levels of FoxP3 expression in various thyroid tissues and lesions. (A) Normal thyroid tissues showed the lowest FoxP3 staining. (B) Goiter lesions presented with intermediate FoxP3 immunostaining. In contrast to the normal thyroid, the goiter cells exhibited increased cytoplasmic and nuclear staining. (C) Follicular adenoma cells demonstrated pronounced cytoplasmic and nuclear FoxP3 immunostaining. (D) Papillary thyroid carcinomas showed strong FoxP3 expression. In particular, increased cytoplasmic expression is evident. (E) Follicular thyroid carcinoma tissues showed faint immunostaining. (F) A papillary thyroid carcinoma with FoxP3+ tumor cells and FoxP3+ lymphocytes. The white arrows show regulatory T lymphocytes infiltrating the malignant tissue. The black arrows show papillary thyroid carcinoma cells with both cytoplasmic and nuclear FoxP3 staining. Magnification = 400x.
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f1-cln_67p483: Different levels of FoxP3 expression in various thyroid tissues and lesions. (A) Normal thyroid tissues showed the lowest FoxP3 staining. (B) Goiter lesions presented with intermediate FoxP3 immunostaining. In contrast to the normal thyroid, the goiter cells exhibited increased cytoplasmic and nuclear staining. (C) Follicular adenoma cells demonstrated pronounced cytoplasmic and nuclear FoxP3 immunostaining. (D) Papillary thyroid carcinomas showed strong FoxP3 expression. In particular, increased cytoplasmic expression is evident. (E) Follicular thyroid carcinoma tissues showed faint immunostaining. (F) A papillary thyroid carcinoma with FoxP3+ tumor cells and FoxP3+ lymphocytes. The white arrows show regulatory T lymphocytes infiltrating the malignant tissue. The black arrows show papillary thyroid carcinoma cells with both cytoplasmic and nuclear FoxP3 staining. Magnification = 400x.

Mentions: The slides were scored independently by two pathologists (JV and FAS), both of whom were blinded to the tumor features. FoxP3 staining was found in both tumor cells and tumor-infiltrating lymphocytes (Figure 1). To quantify the FoxP3 staining, a tumor cell was considered positive for FoxP3 when an unambiguous brown staining was observed in its cytoplasm or nucleus. Each tissue spot was visually evaluated to estimate the percentage of positive tumor cells and the intensity of the staining. The percentage of positive cells was classified as one of the following: 0 = no positive cells; 1 = up to 10% positive cells; 2 = 10 to 30% positive cells; and 3 = more than 30% positive cells. For statistical purposes, the cases with scores of 0 were defined as negative, and the cases with scores from 1 to 3 were defined as positive.


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)

Different levels of FoxP3 expression in various thyroid tissues and lesions. (A) Normal thyroid tissues showed the lowest FoxP3 staining. (B) Goiter lesions presented with intermediate FoxP3 immunostaining. In contrast to the normal thyroid, the goiter cells exhibited increased cytoplasmic and nuclear staining. (C) Follicular adenoma cells demonstrated pronounced cytoplasmic and nuclear FoxP3 immunostaining. (D) Papillary thyroid carcinomas showed strong FoxP3 expression. In particular, increased cytoplasmic expression is evident. (E) Follicular thyroid carcinoma tissues showed faint immunostaining. (F) A papillary thyroid carcinoma with FoxP3+ tumor cells and FoxP3+ lymphocytes. The white arrows show regulatory T lymphocytes infiltrating the malignant tissue. The black arrows show papillary thyroid carcinoma cells with both cytoplasmic and nuclear FoxP3 staining. Magnification = 400x.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-cln_67p483: Different levels of FoxP3 expression in various thyroid tissues and lesions. (A) Normal thyroid tissues showed the lowest FoxP3 staining. (B) Goiter lesions presented with intermediate FoxP3 immunostaining. In contrast to the normal thyroid, the goiter cells exhibited increased cytoplasmic and nuclear staining. (C) Follicular adenoma cells demonstrated pronounced cytoplasmic and nuclear FoxP3 immunostaining. (D) Papillary thyroid carcinomas showed strong FoxP3 expression. In particular, increased cytoplasmic expression is evident. (E) Follicular thyroid carcinoma tissues showed faint immunostaining. (F) A papillary thyroid carcinoma with FoxP3+ tumor cells and FoxP3+ lymphocytes. The white arrows show regulatory T lymphocytes infiltrating the malignant tissue. The black arrows show papillary thyroid carcinoma cells with both cytoplasmic and nuclear FoxP3 staining. Magnification = 400x.
Mentions: The slides were scored independently by two pathologists (JV and FAS), both of whom were blinded to the tumor features. FoxP3 staining was found in both tumor cells and tumor-infiltrating lymphocytes (Figure 1). To quantify the FoxP3 staining, a tumor cell was considered positive for FoxP3 when an unambiguous brown staining was observed in its cytoplasm or nucleus. Each tissue spot was visually evaluated to estimate the percentage of positive tumor cells and the intensity of the staining. The percentage of positive cells was classified as one of the following: 0 = no positive cells; 1 = up to 10% positive cells; 2 = 10 to 30% positive cells; and 3 = more than 30% positive cells. For statistical purposes, the cases with scores of 0 were defined as negative, and the cases with scores from 1 to 3 were defined as positive.

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