PAX8 and peroxisome proliferator-activated receptor gamma 1 gene expression status in benign and malignant thyroid tissues

Ludovic Lacroix, Caterina Mian, Thierry Barrier, Monique Talbot, Bernard Caillou, Martin Schlumberger, Jean Michel Bidart

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    Résumé

    Objective: Genetic alterations involving the thyroid transcription factor PAX8 and the peroxisome proliferator-activated receptor gamma 1 (PPARγ1) 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-PPARγ1 rearrangement and the expression of the PAX8 and PPARγ transcripts. Methods: Using RT-PCR followed by sequencing PCR products, PAX8-PPARγ1 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 PPARγ transcripts in follicular carcinomas presenting the rearrangement. Interestingly, the level of PPARγ 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 PPARγ and PAX8 gene expression may explain the poorly differentiated histotype of follicular carcinomas harboring the translocation. Immunohistochemistry showed that nuclear PPARγ staining was weak in normal tissues, adenomas, papillary carcinomas and in some follicular carcinomas, and strong in the follicular carcinomas positive for the PAX8-PPARγ1 translocation, but also in some follicular tumors in which no translocation could be evidenced. Conclusion: These observations confirm that the PAX8-PPARγ1 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.

    langue originaleAnglais
    Pages (de - à)367-374
    Nombre de pages8
    journalEuropean Journal of Endocrinology
    Volume151
    Numéro de publication3
    Les DOIs
    étatPublié - 1 sept. 2004

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