Expression of estrogen and androgen receptors in differentiated thyroid cancer: an additional criterion to assess the patient’s risk Flavia Magri, Valentina Capelli, Mario Rotondi, Paola Leporati, Luigi La Manna 1 , Rubina Ruggiero 1 , Alberto Malovini 2 , Riccardo Bellazzi 3 , Laura Villani 4 and Luca Chiovato Units of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri IRCCS, University of Pavia, 27100 Pavia, Italy 1 Department of General and Mininvasive Surgery and 2 Laboratorio di Informatica e Sistemistica per la Ricerca Clinica, Fondazione Salvatore Maugeri IRCCS, 27100 Pavia, Italy 3 Laboratorio di Informatica Biomedica, Dipartimento di Ingegneria Industriale e dell’Informazione, Universita ` di Pavia, 27100 Pavia, Italy 4 Units of Pathology and Cytology, Fondazione Salvatore Maugeri IRCCS, University of Pavia, 27100 Pavia, Italy (Correspondence should be addressed to L Chiovato; Email: luca.chiovato@fsm.it) Abstract Estrogen receptor (ER) and androgen receptor (AR) may be expressed in thyroid tumors, but their prognostic role is controversial. We investigated whether ER and AR expressions could confer a more aggressive phenotype to thyroid tumors. We enrolled 91 patients (13 males and 78 females, mean age 49.3G14.8 years) bearing small (T1 in the 2006 TNM system) differentiated thyroid cancers (DTC). Thirty-eight tumors were incidental histological findings. Using immunohisto- chemistry, we evaluated ERa, ERb, and AR expressions in tumors and in its correspondent extra-tumor parenchyma. In tumors, 13 (16.7%) women and one (7.7%) man expressed ERa; 42 (53.8%) women and six (46%) men expressed ERb; and 16 (20.5%) women and three (23.1%) men expressed AR. In normal thyroid parenchymas, ERb was expressed in 52 (66.7%) women and nine (69.2%) men, ERa in three (3.8%) women, and AR in 13 (16.7%) women. Compared with normal thyroid parenchyma, tumors gained ERa and lost ERb expressions. Incidental cancers were more commonly ERa(K) than ERa(C) (47.7 vs 14.3%, PZ0.037). Postsurgical serum thyroglobulin was higher in ERa(C) tumors than in the ERa(K) tumors (PZ0.04). ERb(K) tumors showed vascular invasion more frequently than the ERb(C) tumors (26.2 vs 4.1%, PZ0.005). AR(C) tumors showed capsular invasion more frequently than the AR(K) tumors (77.8 vs 46.6%, PZ0.014). In conclusion, ERa positivity, ERb negativity, and AR expressions are associated with a more aggressive phenotype of small T1-DTC. ER and AR expressions may represent an additional criterion in deciding whether to perform radioiodine ablation in these tumors. Endocrine-Related Cancer (2012) 19 463–471 Introduction Steroid hormones (SHs) are an important class of cell regulators (Kumar & Thompson 1999, Simoncini & Genazzani 2003). Their biological effects are mediated by a wide spectrum of ligand-dependent intracellular transcription factors (the SH receptors (SHRs)), which include estrogen receptor (ER), androgen receptor (AR), progesterone receptor, glucocorticoid receptor, and mineralocorticoid receptor (Stanisic et al. 2010). A role for SHs in the development and progression of human cancer has been observed, each SH being involved in a specific subset of neoplasm (Ahmad & Kumar 2011). Cumulative exposure to estrogens plays a role in the development, growth, and progression of breast cancer (Badve & Nakshatri 2009), while androgens are essential for the initiation and pro- gression of prostate cancer (Heinlein & Chang 2004). SHRs and their ligands may also be involved in the Endocrine-Related Cancer (2012) 19 463–471 Endocrine-Related Cancer (2012) 19 463–471 1351–0088/12/019–463 q 2012 Society for Endocrinology Printed in Great Britain DOI: 10.1530/ERC-11-0389 Online version via http://www.endocrinology-journals.org Downloaded from Bioscientifica.com at 11/15/2021 07:51:21AM via free access