PMID- 26318038
OWN - NLM
STAT- MEDLINE
DCOM- 20160822
LR  - 20210816
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 29
DP  - 2015 Sep 29
TI  - Nuclear estrogen receptor-alpha expression is an independent predictor of recurrence 
      in male patients with pT1aN0 lung adenocarcinomas, and correlates with regulatory 
      T-cell infiltration.
PG  - 27505-18
LID - 10.18632/oncotarget.4752 [doi]
AB  - BACKGROUND: Tumor biology of estrogen receptor-alpha (ERalpha) and progesterone receptor 
      (PR) has been studied in breast cancers. However, clinical impact in lung cancer 
      remains controversial. In our study, we investigate whether ERalpha 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 ERalpha 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-12Rbeta2 were 
      performed. Cumulative incidence of recurrence (CIR) analysis was used to estimate 
      probability of recurrence. RESULTS: Nuclear ERalpha expression was observed in 157 
      (17%) patients and presented more frequently in females (P = 0.038) and smaller 
      tumors (P = 0.019). Nuclear ERalpha expression was not identified in mucinous tumors. 
      In pT1a patients, 5-year CIR of patients with ERalpha-positive tumors was 
      significantly higher (5-year CIR, 20%) than those with ERalpha-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 ERalpha expression was an 
      independent predictor of recurrence (hazard ratio = 2.27; P = 0.030). In pT1a 
      patients, nuclear ERalpha expression positively correlated with tumoral FoxP3+ 
      lymphocytes (P < 0.001), FoxP3/CD3 index (P < 0.001), and IL-7R (P = 0.022). 
      CONCLUSIONS: Nuclear ERalpha expression is an independent predictor of recurrence in 
      pT1a lung adenocarcinomas and correlates with poor prognostic immune 
      microenvironments.
FAU - Kadota, Kyuichi
AU  - Kadota K
AD  - Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 
      New York, NY, USA.
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
AD  - Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, 
      Kagawa, Japan.
FAU - Eguchi, Takashi
AU  - Eguchi T
AD  - Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 
      New York, NY, USA.
FAU - Villena-Vargas, Jonathan
AU  - Villena-Vargas J
AD  - Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 
      New York, NY, USA.
FAU - Woo, Kaitlin M
AU  - Woo KM
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Sima, Camelia S
AU  - Sima CS
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Jones, David R
AU  - Jones DR
AD  - Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 
      New York, NY, USA.
FAU - Travis, William D
AU  - Travis WD
AD  - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 
      USA.
FAU - Adusumilli, Prasad S
AU  - Adusumilli PS
AD  - Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 
      New York, NY, USA.
AD  - Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, 
      NY, USA.
LA  - eng
GR  - U54 CA137788/CA/NCI NIH HHS/United States
GR  - P50 CA086438/CA/NCI NIH HHS/United States
GR  - R21 CA164585-01A1/CA/NCI NIH HHS/United States
GR  - T32 CA009501/CA/NCI NIH HHS/United States
GR  - R21 CA164568-01A1/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P50 CA086438-13/CA/NCI NIH HHS/United States
GR  - R01 CA136705-06/CA/NCI NIH HHS/United States
GR  - R01 CA136705/CA/NCI NIH HHS/United States
GR  - R21 CA164585/CA/NCI NIH HHS/United States
GR  - R21 CA164568/CA/NCI NIH HHS/United States
GR  - P01 CA129243/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (CD3 Complex)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (IL12RB2 protein, human)
RN  - 0 (IL7 protein, human)
RN  - 0 (Interleukin-7)
RN  - 0 (Receptors, Interleukin-12)
RN  - 0 (Receptors, Progesterone)
SB  - IM
MH  - Adenocarcinoma/diagnosis/*metabolism/pathology
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD3 Complex/metabolism
MH  - Cell Nucleus/metabolism
MH  - Estrogen Receptor alpha/*metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-7/metabolism
MH  - Lung Neoplasms/diagnosis/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Neoplasm Recurrence, Local
MH  - Prognosis
MH  - Receptors, Interleukin-12/metabolism
MH  - Receptors, Progesterone/metabolism
MH  - T-Lymphocytes/cytology
MH  - Young Adult
PMC - PMC4695005
OTO - NOTNLM
OT  - adenocarcinoma
OT  - estrogen receptor
OT  - lung
OT  - recurrence
OT  - regulatory T-cell
COIS- CONFLICTS OF INTEREST All authors have no conflicts of interest to disclose.
EDAT- 2015/09/01 06:00
MHDA- 2016/08/23 06:00
PMCR- 2015/09/29
CRDT- 2015/08/31 06:00
PHST- 2015/05/07 00:00 [received]
PHST- 2015/07/17 00:00 [accepted]
PHST- 2015/08/31 06:00 [entrez]
PHST- 2015/09/01 06:00 [pubmed]
PHST- 2016/08/23 06:00 [medline]
PHST- 2015/09/29 00:00 [pmc-release]
AID - 4752 [pii]
AID - 10.18632/oncotarget.4752 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Sep 29;6(29):27505-18. doi: 10.18632/oncotarget.4752.