Loss of Estrogen Receptor Beta Expression in Follicular Thyroid Carcinoma Predicts Poor Outcome

Background: Well-differentiated follicular thyroid carcinomas (FTCs) usually act indolently, while aggressively acting tumors are difficult to detect early enough. Estrogen receptors (ERs) have prognostic significance in many cancers. Thyroid diseases, including neoplasms, are associated with the female sex. The prognostic significance of ERs in FTCs has not been reported previously. Methods: We studied the role of ER alpha and ER beta in 83 cases of follicular thyroid adenomas (FTA) and 43 FTC cases, including seven cases of poorly differentiated FTC, obtained from the Department of Surgery, Helsinki University Central Hospital between 1990 and 2009. Patient follow-up was conducted until March 2011. Expression of ER alpha, ER beta, and MIB-1/Ki-67 was investigated by immunohistochemistry and correlated with clinicopathological characteristics, including survival. Results: Two major observations were apparent. First, ER beta expression was significantly higher in FTA than in FTC, and it was a stronger differential diagnostic marker than MIB-1/Ki-67. Second, low ER beta expression correlated with poor survival in FTC. All cancer-specific deaths due to FTC were among low ER beta-score patients. Conclusion: ER beta is a differential marker for malignancy and could thus be used as a preoperative tool. FTC patients with a low ER beta score need more thorough follow-up and may benefit from more aggressive treatment.