Association between estrogen receptor-beta expression and epidermal growth factor receptor mutation in the postoperative prognosis of adenocarcinoma of the lung.
OBJECTIVE
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.


METHODS
This study evaluated 447 resected primary lung adenocarcinoma specimens. The expression of ERalpha and ERbeta was evaluated with an immunohistochemical method. The EGFR mutation was evaluated with polymerase chain reaction.


RESULTS
A strong cytoplasmic expression of ERalpha and nuclear expression of ERbeta were detected in 49.4% and 48.5% of all patients, respectively. A strong nuclear expression of ERbeta 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 ERalpha was found.


CONCLUSIONS
A strong nuclear expression of ERbeta correlates with EGFR mutations, and its favorable prognostic significance was influenced by the EGFR mutations in adenocarcinoma of the lung.
Nose
Naohiro
N
Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan. pencil@med.uoeh-u.ac.jp
Sugio
Kenji
K
Oyama
Tsunehiro
T
Nozoe
Tadahiro
T
Uramoto
Hidetaka
H
Iwata
Teruo
T
Onitsuka
Takamitsu
T
Yasumoto
Kosei
K
D000230:Adenocarcinoma / Q000401:mortality* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D066246:ErbB Receptors / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000032:analysis; D047629:Estrogen Receptor beta / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D066246:ErbB Receptors