Correlation of increased tumor expression of estrogen receptor alpha mRNA and low aromatase protein ratio with prognosis in resected non-small cell lung cancer (NSCLC).

Abstract

e21009 Background: Although several studies have shown the presence of estrogen receptors (ERs) in lung tumors, published reports show inconsistent conclusions. Biological role of ER-α, ER-β and aromatase in the development of NSCLC is unclear. Aim of this study was to investigate the prognostic value of ERs and aromatase mRNA-protein concentration in resected NSCLC. Methods: Lung tumor and normal lung were analyzed for expression of ER-α, ER-β and aromatase using a 7900HT Applied Biosystem Fast PCR System. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed for the detection of ER and aromatase expression using RNA from lung cancer tissues immediately submerged in RNA Later (Qiagen) after surgery. Aromatase protein was detected with an enzyme-linked immunosorbent assay kit for human aromatase (USCN Life Science). Results: We included 96 patients (80 male/16 female) with resected NSCLC; 51% adenocarcinoma, 43% squamous, 6% others. Pathological stages: 43% I, 33% II, 22% III and 2% IV. Mean expression of ER-α in normal lung was significantly higher than in lung tumor (0.1554 vs. 0.1182, p < 0.0001). Tumoral expression of ER-β inversely correlated with cigarette consumption in current smokers (p=0.046). Patients with the highest values of tumoral ER-α mRNA had better overall survival than those with the lowest values (< p50 =107 weeks >p50 = 139 weeks; p= 0.037). Aromatase protein mean concentration in tumor lung was significantly higher than in normal lung (10.411 vs. 2.125, p<0.0001). Aromatase protein ratio, tumoral concentration/normal tissue concentration, was significantly linked to overall survival (p=0.024; Exp (B) =1.010; 95% CI Exp (B) = 1.001-1.020), showing that a lower aromatase protein ratio is associated with better overall survival. Conclusions: We report a significant association between quantitative expression of mRNA ER-α and overall survival in tumor of resected NSCLC. We define the relationship between tumoral/ normal tissue aromatase protein ratio and overall survival. A better understanding of estrogen action in lung cancer could provide the basis for future targeted therapies.