Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.

Context: A subset of thyroid carcinomas expresses an oncogenic PAX8-PPARγ fusion protein (PPFP). The PPARγ/PPFP ligand pioglitazone is highly therapeutic in a transgenic mouse model of PPFP thyroid carcinoma, but whether pioglitazone is therapeutic in patients with PPFP thyroid carcinoma is unknown.

Case Description: Tumor blocks from forty patients with progressive thyroid cancer despite standard of care therapy were screened for PPFP, and the tumor from only one patient (2.5%) was positive. The patient had a 6.0 cm acetabular soft tissue metastasis from Hurthle cell carcinoma causing severe pain on weight bearing, and a serum thyroglobulin level of 1974 ng/mL. After 24 weeks of therapy with pioglitazone, the metastasis was 3.9 cm, the thyroglobulin was 49.4 ng/mL and the patient was pain free. Thirteen months after discontinuing pioglitazone, the metastasis was 3.6 cm, the thyroglobulin was 4.7 ng/mL and the patient remained pain free.

Conclusions: Pioglitazone may be therapeutic in patients with PPFP thyroid cancer. However, thyroid cancers that are progressive despite standard of care therapy appear to only rarely express PPFP.