Background: The incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance.
Methods: Immunohistochemical staining of thyroid tissue sections was performed to detect ER expression in female patients with PTC (n =89) and nodular thyroid goiter (NTG; n =30) using the Elivision™ plus two-step system. The relationships between ER subtype expression and clinicopathological/biological factors were further analyzed.
Results: The positive percentage and expression levels of ERα were significantly higher in female PTC patients of reproductive age (18-45 years old; n =50) than age-matched female NTG patients (n =30), while ERβ1 exhibited the opposite pattern. There was no difference in ERα or ERβ1 expression between female PTC patients of reproductive age and those of advanced reproductive age (>45 years old; n =39). In the female PTC patients of reproductive age, ERα expression level was positively correlated with that of Ki-67, while ERβ1 was negatively correlated with mutant P53. Furthermore, more patients with exclusively nuclear ERα expression had extrathyroidal extension (ETE) as compared with those with extranuclear ERα localization. VEGF expression was significantly decreased in female PTC patients of reproductive age with only nuclear ERβ1 expression when compared with those with extranuclear ERβ1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERβ1 expression showed any correlation with that of Ki-67, mutant P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases.
Conclusions: The differential expression patterns of the two ER subtypes between PTC and NTG indicate that ERα may be a useful immunohistochemical marker for differential diagnosis of PTC. The associations of ER subtype expression with Ki-67, mutant P53, VEGF expression and ETE in female PTC patients of reproductive age suggest that estrogen-activated ERα may mediate stimulatory effects on PTC growth and progression whereas ERβ1 has some inhibitory actions.