PAX8 and peroxisome proliferator-activated receptor gamma 1 gene expression status in benign and malignant thyroid tissues.
OBJECTIVE
Genetic alterations involving the thyroid transcription factor PAX8 and the peroxisome proliferator-activated receptor gamma 1 (PPARgamma1) genes have been described in thyroid neoplasms. We investigated in a series of thyroid samples, including 14 normal, 13 hyperfunctioning tissues, 26 follicular adenomas, 21 follicular and 41 papillary carcinomas, both the frequency of the PAX8-PPARgamma1 rearrangement and the expression of the PAX8 and PPARgamma transcripts.


METHODS
Using RT-PCR followed by sequencing PCR products, PAX8-PPARgamma1 translocation was not detected in benign tissues nor in papillary carcinomas and was detected in 4 (19%) of 21 follicular carcinomas and in one (4%) of 26 follicular adenomas.


RESULTS
Specific real-time quantitative RT-PCR (Q RT-PCR) methods detected high levels of PPARgamma transcripts in follicular carcinomas presenting the rearrangement. Interestingly, the level of PPARgamma transcripts was significantly decreased in papillary carcinomas in comparison with those found in benign adenomas and follicular carcinomas. Finally, PAX8 gene expression was decreased in both papillary and follicular thyroid carcinomas, and in these tumors to the same extent in the presence or absence of the rearrangement. These alterations in both PPARgamma and PAX8 gene expression may explain the poorly differentiated histotype of follicular carcinomas harboring the translocation. Immunohistochemistry showed that nuclear PPARgamma staining was weak in normal tissues, adenomas, papillary carcinomas and in some follicular carcinomas, and strong in the follicular carcinomas positive for the PAX8-PPARgamma1 translocation, but also in some follicular tumors in which no translocation could be evidenced.


CONCLUSIONS
These observations confirm that the PAX8-PPARgamma1 translocation characterizes a subset of thyroid follicular carcinomas but is not a specific marker of carcinoma and that its frequency is lower than that initially reported. Finally, immunohistochemistry is not a reliable method for the specific detection of the translocation, that can be specifically evidenced by Q RT-PCR.
Lacroix
Ludovic
L
CNRS UMR 8125-Commissariat a l'Energie Atomique, LRC29V, and Department of Clinical Biology, Institut Gustave-Roussy, 94805 Villejuif Cedex, France.
Mian
Caterina
C
Barrier
Thierry
T
Talbot
Monique
M
Caillou
Bernard
B
Schlumberger
Martin
M
Bidart
Jean-Michel
JM
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002291:Carcinoma, Papillary / Q000235:genetics / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000503:physiopathology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / 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; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors