title: Retinoid acid receptor expression is helpful to distinguish between adenoma and well-differentiated carcinoma in the thyroid.
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.
authors: Department of Pathology, CHU, Nancy, France. g.gauchotte@chu-nancy.fr
authors: Guillaume
authors: G
authors: Gauchotte
authors: Stéphanie
authors: S
authors: Lacomme
authors: Lydia
authors: L
authors: Brochin
authors: Benjamin
authors: B
authors: Tournier
authors: Virginie
authors: V
authors: Cahn
authors: Nathalie
authors: N
authors: Monhoven
authors: Françoise
authors: F
authors: Piard
authors: Marc
authors: M
authors: Klein
authors: Nadine
authors: N
authors: Martinet
authors: Cécile
authors: C
authors: Rochette-Egly
authors: Jean-Michel
authors: JM
authors: Vignaud
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008745:Methylation; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C533416:RARB2 protein, human; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D054840:Retinol-Binding Proteins, Cellular; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase
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