title: Prognostic significance of aromatase and estrogen receptor beta expression in EGFR wild-type lung adenocarcinoma.
abstract: OBJECTIVE
  Based on recent findings of aromatase and estrogen receptor beta (ERβ) expression in non-small-cell lung cancer, we assessed the clinicopathological and prognostic significance of aromatase and ERβ expression and their relationship to epidermal growth factor receptor (EGFR) mutation in lung adenocarcinoma.
  
  
  METHODS
  We evaluated 150 resected primary lung adenocarcinoma specimens. Expression of aromatase, ERα, ERβ, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was evaluated by immunostaining, and EGFR and KRAS mutations were analyzed. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method.
  
  
  RESULTS
  Expression of aromatase, ERα, ERβ, PR, and HER2 was detected in 88.0%, 1.3%, 79.3%, 2.7%, and 39.3% of specimens, respectively. In patients with EGFR wild-type lung adenocarcinoma, high aromatase expression was an independent predictor of poor OS (hazard ratio [HR]=2.638; 95% confidence interval [CI], 1.173-5.936; P=.019) and RFS (HR=2.505; 95% CI, 1.154-5.434; P=.020). Positive ERβ expression was also an independent predictor of poor RFS (HR=4.013; 95% CI, 1.219-13.207; P=.022). Furthermore, high aromatase expression was a significant predictor of poor survival only in females (OS, P=.010; RFS, P=.007), whereas positive ERβ expression was an important predictor of poor survival only in males (OS, P=.073; RFS, P=.051). No prognostic significance was observed in patients with EGFR mutations.
  
  
  CONCLUSIONS
  Our findings suggest that EGFR wild-type lung adenocarcinoma is an estrogen-dependent carcinoma, and aromatase expression and ERβ expression are potent prognostic markers for EGFR wild-type lung adenocarcinoma.
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kakegawa
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ohtaki
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Toshiteru
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Horiguchi
authors.affiliation: Department of Division of Diagnostic Pathology, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Graduate School of Medicine, Gunma University 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
keywords: Aromatase; EGFR mutation; estrogen receptor beta (ERβ); estrogen signaling pathway; lung adenocarcinoma