Estrogen Receptor Alpha and Beta Are Prognostic Factors in Non-small Cell Lung Cancer

Purpose: Estrogen receptor-alpha (ER-alpha) and -beta (ER-beta) play important roles in the carcinogenesis of breast tumors. Similarly, there have been several reports of ER expression in lung cancers, but the results have not been consistent, and the receptors' prognostic value remains unclear. Our goal was to investigate ER expression in non-small cell lung cancer (NSCLC) and to assess whether their expression correlates with prognosis.

Experimental Design: ER expression was examined using immunohistochemical methods with sections from 132 resected NSCLC specimens. Kaplan-Meier survival curves were analyzed to determine the significance of ER expression in the prognosis of NSCLC patients.

Results: ER-alpha was detected in the cytoplasm of 73% of the specimens analyzed, whereas ER-beta was detected in the nucleus of 51%. ER-alpha expression correlated with poorer overall survival (P < 0.001), as did the absence of ER-beta expression (P = 0.048). Likewise, at histopathologic stage I, ER-alpha expression (P = 0.028) or the absence of ER-beta (P = 0.037) correlated with a poorer prognosis, and ER-alpha(+)ER-beta(-) patients had a significantly worse prognosis than ER-alpha(-)ER-beta(+) patients (P = 0.00007). Multivariate Cox regression analysis revealed the absence of ER-beta to be an independent factor predictive of poor disease outcome (hazard ratio, 1.9; 95% confidence interval, 1.1-3.4; P = 0.0264).

Conclusions: ER-alpha expression and the absence of ER-beta expression are associated with a poorer prognosis among NSCLC patients. In particular, the absence of ER-beta could serve as a marker identifying patients at high risk even at an early clinical stage.