Dataset Information

Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.

ABSTRACT:

Context

A subset of thyroid carcinomas expresses an oncogenic paired box 8 (PAX8) and peroxisome proliferator activated receptor γ (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 40 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 Hürthle cell carcinoma that caused severe pain on weight bearing and had a serum thyroglobulin level of 1974 ng/mL. After 24 weeks of therapy with pioglitazone, the metastatic lesion was 3.9 cm, the thyroglobulin level was 49.4 ng/mL, and the patient was pain-free. Thirteen months after discontinuation of pioglitazone, the metastatic lesion was 3.6 cm, the thyroglobulin level 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.

SUBMITTER: Giordano TJ

PROVIDER: S-EPMC6456920 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.

Giordano Thomas J TJ Haugen Bryan R BR Sherman Steven I SI Shah Manisha H MH Caoili Elaine M EM Koenig Ronald J RJ

The Journal of clinical endocrinology and metabolism 20180401 4

<h4>Context</h4>A subset of thyroid carcinomas expresses an oncogenic paired box 8 (PAX8) and peroxisome proliferator activated receptor γ (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.<h4>Case description</h4>Tumor blocks from 40 patients with progressive thyroid cancer despite standard-of-care therapy were sc ...[more]

PMID: 29373711

Similar Datasets

Project description:BackgroundPAX8/PPARγ rearrangement is a common genetic alteration in follicular thyroid carcinoma (FTC) and has been reported with variable frequency in papillary thyroid carcinoma (PTC). The diagnostic and phenotypic features of thyroid nodules positive for PAX8/PPARγ on preoperative examination are not well understood.MethodsThe prevalence of PAX8/PPARγ rearrangement was analyzed in a series of 2015 consecutive thyroid nodules that underwent molecular analysis on cytology specimens and in 446 surgically removed PTCs. For all PAX8/PPARγ positive cases, cytology and surgical pathology slides were examined and the available clinical records were reviewed.ResultsTwenty-two PAX8/PPARγ rearrangements were identified, including 16 detected preoperatively and 6 postoperatively. The incidence of PAX8/PPARγ in PTC was 1.1%. Cytologically, most of these nodules were diagnosed as a follicular neoplasm (73%), followed by the diagnosis of atypia of undetermined significance (19%), and none of the cases was diagnosed as cytologically malignant. All nodules with PAX8/PPARγ detected preoperatively and surgical follow-up available were found to be malignant, among which the most common diagnosis was the encapsulated follicular variant of PTC. Overall, among 20 PAX8/PPARγ-positive tumors that were surgically excised, 17 (85%) were PTC and 3 (15%) were FTC. On follow-up available for 17 patients (mean, 22.4 months), 16 PAX8/PPARγ-positive cancers showed no evidence of biochemical or structural recurrence, whereas 1 patient with FTC developed bone metastasis.ConclusionsIn this series, PAX8/PPARγ rearrangement found in thyroid nodules had a 100% predictive value for differentiated thyroid cancer, and was more predictive of PTC than FTC. However, almost all PTC carrying PAX8/PPARγ were encapsulated follicular-pattern tumors, distinguished from FTC only by nuclear features. Although most tumors carrying this mutation appear to be clinically indolent, at least on short-term follow-up, distant metastasis can develop from FTC positive for PAX8/PPARγ.

Dataset Information

Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.

Context

Case description

Conclusions

Publications

Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma.

Similar Datasets

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