Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

Background: Thyroid cancer is highly prevalent in women during the fertile age, which suggests a possible impact of hormonal and reproductive factors. Methods: We studied the expression of estrogen receptor a (ER alpha or ESR1) and progesterone receptor (PR or PGR) in 182 female and male patients with papillary thyroid cancer and correlated it to clinical and molecular features. Results: ER alpha and PR expression was found in 66.5 and 75.8% of patients respectively and was significantly correlated with larger tumor size and with a non-incidental diagnosis. Moreover, a trend toward a higher prevalence of local metastases was observed in ER-and PR-expressing tumors, which possibly indicates a more aggressive behavior. Interestingly, the occurrence of the 'receptor conversion' phenomenon, which has already been reported to have a negative prognostic effect in breast cancer, was demonstrated for the first time in thyroid tumors. Indeed, almost all of the ER alpha-positive primary tumors analyzed had ER alpha-negative metastatic lymph nodes. At the genetic analyses, BRAF V600E mutation was detected in 23.2% of the tumors and had a higher prevalence in larger tumors and in those with a stronger ER alpha or PR staining. Conclusions: The whole of the findings reported in the present study argue for an association between ER alpha and PR sex hormone receptor expression and a more aggressive presentation. Although no impact on outcome was found, the evaluation of ER alpha and PR receptor expression could add insights into the biological behavior of tumors and could modify the follow-up, particularly in fertile women affected with persistent disease.