Peroxisome Proliferator Activated Receptor Gamma Immunohistochemical Expression in Human Papillary Thyroid Carcinoma Tissues. Possible Relationship to Lymph Node Metastasis

Abstract

Background: Peroxisome proliferator activated receptor gamma (PPARγ) involvement in thyroid tumorigenesis has recently been studied, especially in follicular neoplasms. Conflicting results concerning the regulation of this receptor in human papillary carcinoma have been reported. Therefore, we quantitatively assessed PPARγ immunohistochemical expression in papillary carcinoma in comparison with other types of thyroid tumors and we evaluated its relationship with clinical criteria of aggressiveness. Materials and Methods: Immunohistochemistry (IHC) was performed on 56 human thyroid papillary carcinomas (PTC), 9 follicular carcinomas (FTC), 20 follicular adenomas (FA) and 18 Hürthle cells adenomas. PTC were divided into subgroups according to some aggressiveness criteria: tumor size, capsular invasion, lymph node metastasis. Immunostaining was semi-quantitatively analyzed using image analysis software. Results: Strong nuclear PPARγ expression was detected in a large number of PTC (42%), similar to that found in FTC (44%) or FA (63%). Only Hürthle cell adenoma showed a significantly lower proportion of PPARγ-positive immunoreactivity (11%, p<0.05). Cases of PTC-associated lymph node metastasis showed a higher percentage of PPARγ-positivity than other case categories (63% vs. 20%), a result which was also noticed when comparing large PTC with infracentimentric tumors (60% vs. 39%, p<0.05). Conclusion: These results, combined with recently published data, suggest that the intense PPARγ immunostaining revealed in PTC could be related to high wtPPARγ gene levels. Moreover, they corroborate a strong relationship between PPARγ expression and tumor progression. PPARγ IHC evaluation is not a valuable differential diagnostic tool for thyroid tumors but it could be a reliable marker of papillary carcinoma aggressiveness and a potential predictor for an eventual therapy by PPARγ agonists.