Research Papers:

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

Kyuichi Kadota _, Takashi Eguchi, Jonathan Villena-Vargas, Kaitlin M. Woo, Camelia S. Sima, David R. Jones, William D. Travis and Prasad S. Adusumilli

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Oncotarget. 2015; 6:27505-27518. https://doi.org/10.18632/oncotarget.4752

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Kyuichi Kadota1,2,5, Takashi Eguchi1, Jonathan Villena-Vargas1, Kaitlin M. Woo3, Camelia S. Sima3, David R. Jones1, William D. Travis2, Prasad S. Adusumilli1,4

1Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

2Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

3Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

4Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA

5Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan

Correspondence to:

Prasad S. Adusumilli, e-mail: adusumip@mskcc.org

Keywords: adenocarcinoma, lung, estrogen receptor, regulatory T-cell, recurrence

Received: May 07, 2015     Accepted: July 17, 2015     Published: July 29, 2015


Background: Tumor biology of estrogen receptor-α (ERα) and progesterone receptor (PR) has been studied in breast cancers. However, clinical impact in lung cancer remains controversial. In our study, we investigate whether ERα 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 ERα 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-12Rβ2 were performed. Cumulative incidence of recurrence (CIR) analysis was used to estimate probability of recurrence.

Results: Nuclear ERα expression was observed in 157 (17%) patients and presented more frequently in females (P = 0.038) and smaller tumors (P = 0.019). Nuclear ERα expression was not identified in mucinous tumors. In pT1a patients, 5-year CIR of patients with ERα-positive tumors was significantly higher (5-year CIR, 20%) than those with ERα-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 ERα expression was an independent predictor of recurrence (hazard ratio = 2.27; P = 0.030). In pT1a patients, nuclear ERα expression positively correlated with tumoral FoxP3+ lymphocytes (P < 0.001), FoxP3/CD3 index (P < 0.001), and IL-7R (P = 0.022).

Conclusions: Nuclear ERα expression is an independent predictor of recurrence in pT1a lung adenocarcinomas and correlates with poor prognostic immune microenvironments.

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