title: Prognostic relevance of estrogen receptor α, β and aromatase expression in non-small cell lung cancer.
abstract: 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.
authors.affiliation: Department of Medical Biology, UiT - The Arctic University of Norway, 9037 Tromso, Norway. Electronic address: kaja.skjefstad@gmail.com.
authors.forename: Kaja
authors.initials: K
authors.lastname: Skjefstad
authors.affiliation: Department of Medical Biology, UiT - The Arctic University of Norway, 9037 Tromso, Norway.
authors.forename: Thea
authors.initials: T
authors.lastname: Grindstad
authors.affiliation: Department of Medical Biology, UiT - The Arctic University of Norway, 9037 Tromso, Norway.
authors.forename: Mehrdad Rakaee
authors.initials: MR
authors.lastname: Khanehkenari
authors.affiliation: Department of Medical Biology, UiT - The Arctic University of Norway, 9037 Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, 9037 Tromso, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Richardsen
authors.affiliation: Department of Clinical Medicine, UiT - The Arctic University of Norway, 9037 Tromso, Norway; Department of Oncology, University Hospital of North Norway, 9037 Tromso, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, 9037 Tromso, Norway; Department of Oncology, University Hospital of North Norway, 9037 Tromso, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kilvaer
authors.affiliation: Department of Clinical Medicine, UiT - The Arctic University of Norway, 9037 Tromso, Norway; Department of Oncology, University Hospital of North Norway, 9037 Tromso, Norway.
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.affiliation: Department of Clinical Medicine, UiT - The Arctic University of Norway, 9037 Tromso, Norway; Department of Oncology, University Hospital of North Norway, 9037 Tromso, Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.affiliation: Department of Medical Biology, UiT - The Arctic University of Norway, 9037 Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, 9037 Tromso, Norway.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: Department of Medical Biology, UiT - The Arctic University of Norway, 9037 Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, 9037 Tromso, Norway.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D001141:Aromatase
keywords: Aromatase; Estrogen; Hormone related cancers; Lung cancer; New biomarkers; Prognosis