Association Between Estrogen Receptor-β Expression and Epidermal Growth Factor Receptor Mutation in the Postoperative Prognosis of Adenocarcinoma of the Lung

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Abstract
Purpose: Adenocarcinoma of the lung unrelated to a smoking habit occurs more frequently in women than men, thus suggesting an association between female hormones and development of these tumors. The aim of this study was to elucidate the correlation between expression of estrogen receptor (ER) and clinicopathologic factors, including a mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR), and prognosis in adenocarcinoma of the lung. Patients and Methods: This study evaluated 447 resected primary lung adenocarcinoma specimens. The expression of ERα and ERβ was evaluated with an immunohistochemical method. The EGFR mutation was evaluated with polymerase chain reaction. Results: A strong cytoplasmic expression of ERα and nuclear expression of ERβ were detected in 49.4% and 48.5% of all patients, respectively. A strong nuclear expression of ERβ was independently associated with the EGFR mutations (odds ratio = 2.947; 95% CI, 1.97 to 4.57; P < .001) and good differentiation (odds ratio = 1.84; 95% CI, 1.21 to 2.80; P = .004) and was correlated with an increasing disease-free survival in patients with EGFR mutations (hazard ratio = 2.18; 95% CI, 1.18 to 4.06; P = .014). However, no prognostic significance was identified in patients without EGFR mutations. No clinicopathologic and/or prognostic significance of a strong expression of cytoplasmic ERα was found. Conclusion: A strong nuclear expression of ERβ correlates with EGFR mutations, and its favorable prognostic significance was influenced by the EGFR mutations in adenocarcinoma of the lung.