Estrogen Receptor Beta and CXCR4/CXCL12 Expression: Differences by Sex and Hormonal Status in Lung Adenocarcinoma
Studies have reported differences in lung cancer behavior between sex and hormonal status that suggest a role of estrogens and estrogen receptor beta (ERβ) in lung carcinogenesis. In some types of hormone-dependent cancer, estrogens may regulate CXCL12/CXCR4 expression through ERβ signaling. High expression of CXCL12/CXCR4 is associated with poor prognosis in lung cancer because it promotes tumor growth and metastasis. Therefore, in this study we investigated whether lung adenocarcinoma tissues from pre- and postmenopausal women and from men exhibit different ERβ, CXCR4/CXCL12 expression and whether this expression is associated with clinicopathological features.Sixty primary tumor samples of lung adenocarcinoma from pre- and postmenopausal women and from men were collected for this study. Thirty samples of healthy lung tissue adjacent to the tumor site were used as controls. ERβ and CXCL12/CXCR4 expression was analyzed by immunohistochemistry. Expression of these proteins was measured by digital image software and compared between sex and hormonal status.Lung adenocarcinomas overexpressed ERβ, CXCR4 and CXCL12 compared to normal lung. Moreover, lung adenocarcinomas from premenopausal women exhibited higher signals for ERβ, CXCL12 and CXCR4 compared to postmenopausal women and to men, who showed lower signals for these proteins. A multivariate analysis revealed a strong association between the immunoreactivity level of ERβ, CXCL12/CXCR4 and both sex and hormonal status, but not with tumor stage and smoking.These results demonstrated that ERβ and CXCL12/CXCR4 expression in lung adenocarcinoma depends on sex and hormonal status, which may partly explain the sex and hormonal differences in lung cancer behavior.