Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome.

ABSTRACT: Steroid hormones and growth factors affect lung cancer, and it is possible they act in concert to influence patient outcome.Primary lung tumors and normal lung tissue were analyzed for expression and localization of estrogen receptor ? and ?-1 (ER? and ER?), aromatase, progesterone receptor (PR), and epidermal growth factor receptor (EGFR).Tumors expressed higher levels of ER? compared to matched normal lung, whereas the reverse was true of PR. High cytoplasmic ER? expression was identified as an independent negative prognostic predictor of overall survival (OS; HR = 1.67), and low total PR was identified as an independent negative predictor of time to progression (TTP; HR = 1.59). After adjusting for stage, age, sex, and smoking, combined high cytoplasmic ER? and low total PR showed enhanced effects on OS (HR = 2.64) and on TTP (HR = 6.02). Further effects on OS were observed when EGFR expression was included (HR = 5.32). Patients with low cytoplasmic ER?, low aromatase, low EGFR, and high total PR had shorter OS than patients with the opposite pattern (HR = 6.60). Contribution of these markers to survival showed no significant sex differences in a multivariable model. ER? was elevated in tumors but was not predictive of survival, and appears to represent a variant ER? protein that is only recognized by a C-terminal antibody.Hormonal and EGFR pathways together may contribute to lung cancer prognosis. Lung tumors with high ER?-1/low PR may define patients with aggressive biology. A validation study is necessary to fully assess the predictive value of these markers.

SUBMITTER: Stabile LP 

PROVIDER: S-EPMC3064257 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature