Nuclear estrogen receptor-a expression is an independent predictor of recurrence in male patients with pT1aN0 lung adenocarcinomas, and correlates with regulatory T-cell infiltration Journal Article

   

Authors:	Kadota, K.; Eguchi, T.; Villena-Vargas, J.; Woo, K. M.; Sima, C. S.; Jones, D. R.; Travis, W. D.; Adusumilli, P. S.
Article Title:	Nuclear estrogen receptor-a expression is an independent predictor of recurrence in male patients with pT1aN0 lung adenocarcinomas, and correlates with regulatory T-cell infiltration
Abstract:	Background: Tumor biology of estrogen receptor-a (ERa) and progesterone receptor (PR) has been studied in breast cancers. However, clinical impact in lung cancer remains controversial. In our study, we investigate whether ERa and PR expression predicts disease recurrence and correlates with immunologic factors in stage I lung adenocarcinoma. Methods: We reviewed patients with pathologic stage I resected lung adenocarcinoma. Tumors were classified according to the IASLC/ATS/ERS classification. Immunostaining of ERa and PR was performed using tissue microarrays (n = 913). Immunostaining of CD3+ and forkhead box P3 (FoxP3)+ lymphocyte infiltration, interleukin-7 receptor (IL-7R), and IL-12Rb2 were performed. Cumulative incidence of recurrence (CIR) analysis was used to estimate probability of recurrence. Results: Nuclear ERa expression was observed in 157 (17%) patients and presented more frequently in females (P = 0.038) and smaller tumors (P = 0.019). Nuclear ERa expression was not identified in mucinous tumors. In pT1a patients, 5-year CIR of patients with ERa-positive tumors was significantly higher (5-year CIR, 20%) than those with ERa-negative tumors (8%; P = 0.018). This difference was statistically significant in males (P = 0.003) but not females (P = 0.55). On multivariate analysis, nuclear ERa expression was an independent predictor of recurrence (hazard ratio = 2.27; P = 0.030). In pT1a patients, nuclear ERa expression positively correlated with tumoral FoxP3+ lymphocytes (P < 0.001), FoxP3/CD3 index (P < 0.001), and IL-7R (P = 0.022). Conclusions: Nuclear ERa expression is an independent predictor of recurrence in pT1a lung adenocarcinomas and correlates with poor prognostic immune microenvironments.
Keywords:	adenocarcinoma; recurrence; lung; estrogen receptor; regulatory t-cell
Journal Title:	Oncotarget
Volume:	6
Issue:	29
ISSN:	1949-2553
Publisher:	Impact Journals
Date Published:	2015-09-29
Start Page:	27505
End Page:	27518
Language:	English
DOI:	10.18632/oncotarget.4752
PROVIDER:	scopus
PUBMED:	26318038
PMCID:	PMC4695005
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84944456128&partnerID=40&md5=fc08849a53ce5a0cf23ec18b8828f54b
Notes:	Export Date: 2 November 2015 -- Source: Scopus

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