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Virchows Archiv

, Volume 462, Issue 6, pp 619–632 | Cite as

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

  • Guillaume GauchotteEmail author
  • Stéphanie Lacomme
  • Lydia Brochin
  • Benjamin Tournier
  • Virginie Cahn
  • Nathalie Monhoven
  • Françoise Piard
  • Marc Klein
  • Nadine Martinet
  • Cécile Rochette-Egly
  • Jean-Michel Vignaud
Original Article

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.

Keywords

Retinoids RAR RXR Promoter methylation Loss of heterozygosity Thyroid cancer 

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Guillaume Gauchotte
    • 1
    • 3
    • 8
    Email author
  • Stéphanie Lacomme
    • 2
  • Lydia Brochin
    • 1
  • Benjamin Tournier
    • 4
  • Virginie Cahn
    • 1
  • Nathalie Monhoven
    • 1
  • Françoise Piard
    • 4
  • Marc Klein
    • 5
  • Nadine Martinet
    • 6
  • Cécile Rochette-Egly
    • 7
  • Jean-Michel Vignaud
    • 1
    • 2
    • 3
  1. 1.Department of PathologyCHUNancyFrance
  2. 2.Centre de Ressources BiologiquesCHUNancyFrance
  3. 3.Medical FacultyINSERM U954NancyFrance
  4. 4.Department of Pathology and Molecular OncologyCHUDijonFrance
  5. 5.Department of Endocrinology, Hôpitaux de BraboisCHUVandoeuvre-lès-NancyFrance
  6. 6.Institut de Chimie de Nice, UMR 7272University of Nice Sophia-AntipolisNiceFrance
  7. 7.Génomique fonctionnelle et cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U964; CNRS, UMR 7104University of StrasbourgIllkirchFrance
  8. 8.Service d’Anatomie et Cytologie Pathologiques, Hôpital CentralCHU de NancyNancyFrance

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