The prevalence and prognostic significance of estrogen receptor beta expression in non-small cell lung cancer

BACKGROUND: Estrogen receptor beta (ERβ) is the predominant estrogen receptor (ER) expressed in non-small cell lung cancer (NSCLC); however, due to methodological disparities among prior studies, the prognostic value of ERβ expression in NSCLC remains unclear. Our objective was to apply improved detection and analysis techniques to assess the prognostic value of ERβ expression in NSCLC. METHODS: A tissue microarray (TMA) was used which contained resected and biopsy specimens from 299 patients diagnosed at a single center with stages I–IV NSCLC. Sections of this array were stained using high-sensitivity fluorescence immunohistochemistry, with the well-validated PPG5/10 monoclonal antibody. Digital images of the stained array slides were analyzed using software-based image analysis, which reported ERβ expression as a continuous variable in different subcellular domains. RESULTS: There were no differences in ERβ expression between male and female patients. High expression of ERβ was not a prognostic factor, but was significantly associated with stage IV disease in both tumor and stroma (P<0.001). In multivariable analysis, a high nuclear/cytoplasmic (N/C) ratio of ERβ expression was significantly associated with shorter overall survival, based on expression in the tumor [hazard ratio (HR): 1.65; 95% confidence interval (CI): 1.25–2.19; P<0.001] and in the stroma (HR: 1.57; 95% CI: 1.16–2.12; P=0.003). CONCLUSIONS: These results suggest that subcellular localization of ERβ, but not absolute expression, is a prognostic factor in NSCLC.