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Retinoid acid receptor expression is helpful to distinguish between adenoma and well-differentiated carcinoma in the thyroid

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Abstract

Retinoid receptors (RRs) play a key role in cell proliferation and differentiation. We characterized the expression of RA receptors and retinoid X receptors (RARs and RXRs) in a series of 111 thyroid tumors and investigated the mechanisms responsible for their deregulation: hypermethylation of the RARB2 promoter, loss of heterozygosity (LOH) in the regions of RARB and RXRA, and altered expression of CRBP1 and enzymes involved in RA biosynthesis (RDH10 and RALDH2). Expression of RALDH2 and RDH10 was conserved in 100 % of adenomas and in 90 and 98 %, respectively, of carcinomas, whereas staining for CRBP1 was decreased in 9 % of FAs and 28 % of carcinomas, mainly anaplastic carcinomas (55 %). We found an abnormal expression of RARA, RARB, RXRA, and RXRB in 67, 69, 66, and 73 %, respectively, of thyroid carcinomas (n = 78) and in 9, 9, 9, and 33 % of follicular adenomas (n = 33) (p < 0.001). An abnormal staining pattern of at least two of these markers had 90 % sensitivity and 91 % specificity for a diagnosis of malignancy. Promoter hypermethylation of RARB2 was observed in some anaplastic carcinomas (14 %). LOH was found to be common at the RARB locus (3p24–3p25) and the RXRA locus (9q34), respectively, in 44 and 55 % of carcinomas and in 27 and 43 % of adenomas. In conclusion, immunohistochemical staining for RARs and RXRs may help in the differential diagnosis between well-differentiated carcinoma and follicular adenoma. Further investigation should be carried out to determine whether the characterization of RR expression might identify patients who could benefit from therapy with RA derivatives.

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Acknowledgments

The authors thank Mrs. Caroline Chapusot (Department of Pathology, CHU Dijon), Mrs. Brigitte Léotard, Ms. Aline Saunier (Department of Genetics, CHU Nancy), Ms. Julie Zinszner (Department of Pathology, CHU Nancy) for technical support, Mr. Marc Soudant (Epidemiology and Clinical Evaluation, CHU Nancy) for statistical analysis, and Mrs. Jacqueline Zevnick for reviewing the manuscript.

Conflict of interest

The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Department of Pathology, CHU, Nancy, France

    Guillaume Gauchotte, Lydia Brochin, Virginie Cahn, Nathalie Monhoven & Jean-Michel Vignaud

  2. Centre de Ressources Biologiques, CHU, Nancy, France

    Stéphanie Lacomme & Jean-Michel Vignaud

  3. Medical Faculty, INSERM U954, Nancy, France

    Guillaume Gauchotte & Jean-Michel Vignaud

  4. Department of Pathology and Molecular Oncology, CHU, Dijon, France

    Benjamin Tournier & Françoise Piard

  5. Department of Endocrinology, Hôpitaux de Brabois, CHU, Vandoeuvre-lès-Nancy, France

    Marc Klein

  6. Institut de Chimie de Nice, UMR 7272, University of Nice Sophia-Antipolis, Nice, France

    Nadine Martinet

  7. Génomique fonctionnelle et cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U964; CNRS, UMR 7104, University of Strasbourg, Illkirch, France

    Cécile Rochette-Egly

  8. Service d’Anatomie et Cytologie Pathologiques, Hôpital Central, CHU de Nancy, 29, avenue du Maréchal De Lattre de Tassigny, 54000, Nancy, France

    Guillaume Gauchotte

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  1. Guillaume Gauchotte
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  9. Nadine Martinet
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  10. Cécile Rochette-Egly
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  11. Jean-Michel Vignaud
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Correspondence to Guillaume Gauchotte.

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Gauchotte, G., Lacomme, S., Brochin, L. et al. Retinoid acid receptor expression is helpful to distinguish between adenoma and well-differentiated carcinoma in the thyroid. Virchows Arch 462, 619–632 (2013). https://doi.org/10.1007/s00428-013-1419-z

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  • DOI: https://doi.org/10.1007/s00428-013-1419-z

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