Quantification of PPARg expression in different thyroid pathologies

Peroxisome proliferator-activated receptor gamma (PPARg) has been shown to exert antiproliferative and re-differentiating effects in various cancers including thyroid malignancy. A PAX-8-PPARg fusion gene has been implicated in the etiology of follicular thyroid cancer, acting as a dominant negative PPARg inhibitor. In addition downregulation of PPARg mRNA and protein expression has recently been described in nonmedullary thyroid cancer. The aim of our study was to evaluate the usefulness of PPARg expression as a marker of differentiation in various thyroid pathologies and functional status.

RNA was extracted from 56 snap frozen samples: 10 cold benign (CTN) and 10 solitary toxic nodules (TTN) and their surrounding normal thyroid tissue, 10 follicular thyroid cancers (FTC) and 6 Graves’ disease (GD) thyroid samples. LightCycler PCR was performed using exon spanning PPARg primers. Results were normalised for b-actin expression. Moreover all samples were screened for presence of the known PAX-8-PPARg fusion genes by RT-PCR. PPARg mRNA expression was demonstrated in all thyroid samples. Similar PPARg expression levels were found in CTN and FTC (PPARg/b-actin ratio: 7.66±72% and 7.34±49% respectively), which were significantly lower than PPARg mRNA expression levels in TTN (10.3±54%). However, when comparing mRNA expression levels in nodules with corresponding normal thyroid tissue of the same patient only marginal (CTN) or no significant differences (TTN) in PPARg expression could be demonstrated. In contrast, PPARg expression was markedly downregulated in GD (2.06±61%). No PAX-8-PPARg fusion gene was detected in the series of 56 thyroid samples. We conclude that there is no clear cut association of PPARg expression with ongoing thyroid tumorigenesis and thus determination of PPARg mRNA expression does not allow reliable early stage distinction of benign and malignant thyroid pathology in an individual patient. In addition our findings are in agreement with the suggestion of PAX-8-PPARg rearrangement being restricted to a subset of follicular thyroid cancers.