Affiliation:
1. Centro de Investigação de Patobiologia Molecular (A.R.M., C.E., S.M., L.G.S., V.L.), 1099-023 Lisboa Codex, Portugal
2. Departamento de Patologia Morfológica (A.L.C., T.P.), Instituto Português de Oncologia Francisco Gentil, 1099-023 Lisboa Codex, Portugal
Abstract
Recently, a translocation t(2;3)(q13;p25), leading to the formation of a chimeric PAX8-peroxisome proliferator-activated receptor (PPAR)γ1 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 1 of PPARγ1 with PPARγ immunohistochemistry to study PAX8-PPARγ1 oncogene activation in FTC (n = 9), FTA (n = 16), PTC (n = 9), anaplastic thyroid carcinomas (n = 4), and multinodular hyperplasias (n = 2). PAX8-PPARγ1 rearrangements were detected by RT-PCR in 5 of 9 (56%) FTC and in 2 of 16 (13%) FTA. By contrast, all cases of PTC, anaplastic thyroid carcinomas, and multinodular hyperplasia were RT-PCR-negative. Diffuse nuclear immunoreactivity for PPARγ was observed in 7 of 9 (78%) FTC, 5 of 16 FTA (31%), and 1 of 9 PTC (11%). Positivity was focal in 3 cases (1 FTC, 1 PTC, and 1 multinodular hyperplasia). Diffuse nuclear staining for PPARγ was present in RT-PCR- negative cases of FTC (n = 3), FTA (n = 3), and PTC (n = 1), suggesting that a different PAX8-PPARγ1 breakpoint, a rearrangement between PPARγ1 and a non-PAX8 partner, or overexpression of the native protein might be present.
Our findings that PAX8-PPARγ1 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.
Subject
Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism
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