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Retinoic acid receptor and retinoid X receptor subtype expression for the differential diagnosis of thyroid neoplasms

Departments of¹ , Endocrinology and Metabolic Diseases C4-R² Pathology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands

(Correspondence should be addressed to J W A Smit; Email: jwasmit{at}lumc.nl)

Background: Although differential expression of retinoic acid receptor (RAR) subtypes between benign and malignant thyroid tissues has been described, their diagnostic value has not been reported.

Aim: To investigate the diagnostic accuracy of RAR and retinoid X receptor (RXR) subtype protein expression for the differential diagnosis of thyroid neoplasms.

Methods: We used a tissue array containing 93 benign thyroid tissues (normal thyroid, multinodular goiter, and follicular adenoma (FA)) and 77 thyroid carcinomas (papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, and follicular variant of PTC (FVPTC)). Immunostaining was done for RAR and RXR subtypes. Staining was analyzed semiquantitatively based on receiver operating curve analyses and using hierarchical cluster analysis.

Results: We found increased expression of cytoplasmic (c) RARA, cRARG, cRXRB and decreased expression of nuclear (n) RARB, nRARG, and nRXRA in thyroid carcinomas compared with benign tissues. We found three proteins differently expressed between FA and FTC and five proteins differentially expressed between FA and FVPTC, with high diagnostic accuracies. Using cluster analysis, the combination of negative staining of membranous RXRB and positive staining for cRXRB had a high positive predictive value (98%) for malignant thyroid disease, whereas the combination of positive nRXRA and negative cRXRB staining had a high predictive value (91%) for benign thyroid lesions.

Conclusion: We conclude that differences in RAR and RXR subtype protein expression may be valuable for the differential diagnosis of thyroid neoplasms. The results of this study and especially the value of cluster analysis have to be confirmed in subsequent studies.