Peroxisome proliferator-activated receptor γ (PPARγ) gene is a nuclear receptor that is involved in thyroid tumourigenesis. Recently, our group has shown that follicular carcinomas underexpressing PPARγ protein are more prone to develop distant metastases, to invade locally, to present poorly differentiated areas and to persist after surgery. Aneuploidy is also observed in some thyroid tumours, particularly in the more advanced cases. The aim of the present study was to investigate the association of PPARγ expression with the degree of differentiation and ploidy status of benign and malignant thyroid neoplasias. DNA cytometric studies, ploidy and S-phase fraction (SPF) determination, and quantitative RT-PCR analysis of molecular markers specific for thyroid follicular cells, namely Tg (thyroglobulin), TSHR (TSH receptor) and NIS (Na+/I− symporter) were compared between thyroid lesions with positive or negative PPARγ protein expression. We observed that PPARγ-negative tissues expressed lower levels of Tg mRNA [4.66x106 a.u. (arbitrary units) ± 1.49x106], and were more frequently aneuploid (36%), and presented higher SPF (3.1%±0.4) than PPARγ-positive samples (Tg mRNA = 2.54x107 a.u. ± 9.72x106, P=0.0006; aneuploidy=8%, P=0.0031; SPF=2.2%±0.2, P=0.0430). A similar trend was also observed for TSHR and NIS mRNA, although not reaching statistical significance. This study showed that underexpression of PPARγ is associated with poor tumour differentiation, aneuploidy and higher cell proliferative activity. Therapies designed to modulate expression of PPARγ may have an impact on the growth of thyroid neoplasias.

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