Expression levels of estrogen receptor beta in conjunction with aromatase predict survival in non-small cell lung cancer

Estrogen signaling pathways may play a significant role in the pathogenesis of non-small cell lung cancers (NSCLC) as evidenced by the expression of aromatase and estrogen receptors (ER alpha and ER beta) in many of these tumors. Here we examine whether ER alpha and ER beta levels in conjunction with aromatase define patient groups with respect to survival outcomes and possible treatment regimens. Immunohistochemistry was performed on a high-density tissue microarray with resulting data and clinical information available for 377 patients. Patients were subdivided by gender, age and tumor histology, and survival data was determined using the Cox proportional hazards model and Kaplan-Meier curves. Neither ER alpha nor ER beta alone was predictor of survival in NSCLC. However, when coupled with aromatase expression, higher ER beta levels predicted worse survival in patients whose tumors expressed higher levels of aromatase. Although this finding was present in patients of both genders, it was especially pronounced in women >= 65 years old, where higher expression of both ER beta and aromatase indicated a markedly worse survival rate than that determined by aromatase alone. Expression of ER beta together with aromatase has predictive value for survival in different gender and age subgroups of NSCLC patients. This predictive value is stronger than each individual marker alone. Our results suggest treatment with aromatase inhibitors alone or combined with estrogen receptor modulators may be of benefit in some subpopulations of these patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.