The expression of estrogen receptors β2, 5 identifies and is associated with Prognosis in non-small cell lung cancer

Estrogens play a pivotal role in the development and progression of non-small lung cancer (NSCLC). With the discovery of estrogen receptor β (ERβ) isoforms, some controversial roles of ERβ were explained adequately in NSCLC. In this study, our aim is to elucidate expression, distribution, and prognostic significance of ERβ 1, 2, 5 in NSCLC. Estrogen receptors β1, 2, 5 protein expression were confirmed by Western-blot analysis in all frozen tissues, and immunohistochemistry (IHC). Nuclear and cytoplasmic staining was evaluated and correlated with histopathologic characteristics, overall survival (OS) and disease-free survival (DFS) via Pearson χ2 square, Kaplan–Meier plots and Cox proportional hazard models. ERβ1 was commonly found in the cytoplasm and was the most abundant isofroms followed by ERβ2 and ERβ5 which were localized in the cytoplasm and nucleus. In contrast to BPL, both in nucleus and cytoplasm, ERβ1, ERβ2, and ERβ5 were over expressed all in NSCLC (P < 0.05). IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ERβ1, ERβ2, and ERβ5 in NSCLC. nERβ1 “nuclear”, cERβ2 and cERβ5 “cytoplasm” were in a negative correlation with the pathological stage and lymph node metastasis. In a Kaplan–Meier analysis, the expression cERβ2 and cERβ5 identified a group of patients with the longest DFS and OS. Cox proportional hazard models revealed that cERβ2 and cERβ5 predicted long time to DFS and OS. This is the first study to uncover the expression of ERβ1, ERβ2, and ERβ5, and show that they were over expressed in NSCLC. Meantime, we find that positive expression of cERβ2 and cERβ5 were in a positive correlation with DFS, and have prognostic values for the progression of NSCLC.