Expression of PAX8-PPAR gamma 1 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)gamma 1 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 PPAR gamma 1 with PPAR gamma immunohistochemistry to study PAX8-PPAR gamma 1 oncogene activation in FTC (n = 9), FTA (n = 16), PTC (n = 9), anaplastic thyroid carcinomas (n = 4), and multinodular hyperplasias (n = 2). PAX8-PPAR gamma 1 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 PPAR gamma 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 PPAR gamma was present in RT-PCR- negative cases of FTC (n = 3), FTA (n = 3), and PTC (n = 1), suggesting that a different PAX8-PPAR gamma 1 breakpoint, a rearrangement between PPAR gamma 1 and a non-PAX8 partner, or overexpression of the native protein might be present. Our findings that PAX8-PPAR gamma 1 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.
Marques
Ana Rita
AR
Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia Francisco Gentil, 1099-023 Lisboa Codex, Portugal.
Espadinha
Carla
C
Catarino
Ana L
AL
Moniz
Sónia
S
Pereira
Teresa
T
Sobrinho
Luís G
LG
Leite
Valeriano
V
D000236:Adenoma / Q000737:chemistry / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors