Critical analysis of the role of immune cells infiltration in prognosis of patients with differentiated thyroid carcinoma

Author(s)

Lucas Leite Cunha

• Document type: Master's Dissertation
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 15-02-2012

Examining board members

Fabiana Granja; Carmen Silvia Passos Lima

• Advisor: Laura Sterian Ward

Abstract

Thyroid cancer is the most common endocrine malignancy. The objective of this project is to investigate the pattern of gene and protein expression of tumors resistant and susceptible to activation of the immune system as well as research evidence tumor evasion mechanisms of the immune response. We investigated 398 patients whose tissue samples were kept in the tissue bank ACCamargo Hospital, São Paulo, with 253 papillary carcinomas, 13 follicular carcinomas and 132 benign tumors. The protein expression profile of tumors was assessed by immunohistochemistry and the infiltration of immune cells was characterized by immunohistochemical markers. Chronic lymphocytic thyroiditis concurrent to cancer was more frequent among women, less aggressive tumors that did not have extra thyroid invasion or metastases at diagnosis, and small tumors smaller than 2 cm. The log-rank test showed that the presence of chronic lymphocytic thyroiditis concurrent to cancer was associated with longer relapse-free. Macrophage infiltration was more frequent among women and was associated with relapse-free survival. The infiltration of CD3+ lymphocytes correlates with malignancy and is associated with the presence of metastases at diagnosis. The infiltration of CD4+ and CD20+ were related to the better prognosis. The infiltration of CD8+ lymphocytes may be a marker of better prognosis. The CD56 protein expression was more frequent among benign tissues and is not associated with prognosis of patients with differentiated thyroid carcinoma. The infiltration of FoxP3+ lymphocytes correlated with less aggressive tumor characteristics. The mRNA expression of B7-H1 was characteristic of malignant tissues and B7-H1 protein could point to a more aggressive behavior of the differentiated thyroid carcinoma. Both the infiltration of Th17 lymphocytes and the myeloid derived suppressor cells were more frequent in malignant tumors, although only the infiltration of Th17 correlated with features of better prognosis. Our data suggest that differentiated thyroid carcinoma is enriched by a number of different immune cells. Probably this infiltration is dependent on the pattern of gene and protein expression of these cancers, a pattern that may reflect the immunogenicity of these tumors. Moreover, the association between these cells and infiltration characteristics of better prognosis, suggests that there is an active immune response against attired differentiated thyroid carcinoma can exert antitumor. (AU)