Prognostic relevance of estrogen receptor α, β and aromatase expression in non-small cell lung cancer

• Published in: Steroids 2016-09, Vol.113, p.5-13
• Main Authors: Skjefstad, Kaja, Grindstad, Thea, Khanehkenari, Mehrdad Rakaee, Richardsen, Elin, Donnem, Tom, Kilvaer, Thomas, Andersen, Sigve, Bremnes, Roy M., Busund, Lill-Tove, Al-Saad, Samer
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aromatase; Aromatase - genetics; Aromatase - metabolism; Biomarkers, Tumor - metabolism; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - physiopathology; Cell Line, Tumor; Estrogen; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - genetics; Estrogen Receptor beta - metabolism; Female; Gene Expression Regulation, Neoplastic; Hormone related cancers; Humans; In Vitro Techniques; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - physiopathology; Male; Middle Aged; New biomarkers; Prognosis; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2016.05.008

•We analyze estrogen receptor (ER) α, β and aromatase (AR) levels in 335 NSCLC cases.•Tumor tissue samples were collected from our patient cohort.•Tissue microarrays were constructed for immunohistochemical analyses.•High ERβ expression in tumor epithelial cells is a negative prognosticator in females.•Patients expressing high AR in tumor epithelia had an unfavorable prognostic outcome. Sex steroids and their receptors are important in the fetal development of normal lung tissue. In addition emerging evidence reveals their significance in lung cancer pathogenesis. This encourages the exploitation of hormone receptors as treatment targets in lung cancer, as it has been successfully used in breast cancer. This study investigates the prognostic impact of estrogen receptor (ER) α and β and the aromatase (AR) enzyme in non-small cell lung cancer (NSCLC) patients. Tumor tissue from 335 NSCLC patients was collected and tissue microarrays (TMAs) were constructed. Immunohistochemical analyses were performed to evaluate the expression of ERα, ERβ and AR in the cytoplasme and nuclei of cells in the tumor epithelial and stromal compartment. By use of survival statistics we investigated the markers impact on disease-specific survival (DSS). Nuclear ERβ expression in tumor epithelial cells in female patients (HR 3.03; 95% CI 1.39–6.61) and tumor cell AR expression in all patients (HR 1.55; 95% CI 1.08–2.23) were significant negative prognostic markers of disease-specific survival in our cohort. High ERβ expression correlates with worse outcome in female patients. Further, patients with high AR expression had an unfavorable prognostic outcome compared with patients expressing low AR levels. These results emphasize the importance of sex steroids role in NSCLC, and, as anti-hormonal drugs are widely available, could lead to the development of novel palliative or even adjuvant treatment strategies in this patient population.