Expression of PAX8-PPARγ1 rearrangements in both follicular thyroid carcinomas and adenomas

Recently, a translocation t(2;3)(q13;p25), leading to the formation of a chimeric PAX8-peroxisome proliferator-activated receptor (PPAR)gamma1 oncogene, was detected in follicular thyroid carcinomas (FTC), but not in follicular thyroid adenomas (FTA), papillary thyroid carcinomas (PTC), or multinodular hyperplasias. However, previous cytogenetic studies have identified the t(2;3)(q13;p25) translocation also in some cases of FTA. In this study, we have combined RT-PCR with primers in exons 4-8 of PAX8 and in exon I of PPARgamma1 with PPARgamma immunohistochemistry to study PAX8-PPARgamma1 oncogene activation in FTC (n = 9), FTA (n = 16), PTC (n = 9), anaplastic thyroid carcinomas (n = 4), and multinodular hyperplasias (n = 2). PAX8-PPARgamma1 rearrangements were detected by RTPCR in 5 of 9 (56%) FTC and in 2 of 16 (13%) FTA. By contrast, all cases of PTC, anaplastic thyroid carcinomas, and multi-nodular hyperplasia were RT-PCR-negative. Diffuse nuclear immunoreactivity for PPARgamma was observed in 7 of 9 (78%) FTC, 5 of 16 FTA (31%), and I of 9 PTC (11%). Positivity was focal in 3 cases (1 FTC, I PTC, and 1 multinodular hyperplasia). Diffuse nuclear staining for PPARy was present in RT-PCR-negative cases of FTC (n = 3), FTA (n = 3), and PTC (n = 1), suggesting that a different PAX8-PPARgamma1 breakpoint, a rearrangement between PPARgamma1 and a non-PAX8 partner, or overexpression of the native protein might be present. Our findings that PAX8-PPARgamma1 rearrangements are present in both follicular carcinomas and adenomas suggest that this oncogene is not a reliable marker to differentiate between FTC and FTA in fine-needle aspiration biopsies of follicular neoplasms of the thyroid.