Cargando…

Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma

There is growing evidence that estrogen receptors (ER) are expressed in lung cancer cells, and are able to interact with the epidermal growth factor receptor (EGFR) signaling pathway. However, data on the association between cytoplasmic ER expression and the response to EGFR-tyrosine kinase inhibito...

Descripción completa

Detalles Bibliográficos
Autores principales: Ding, Xiaosheng, Li, Li, Tang, CHuanhao, Meng, Chao, Xu, Weiran, Wei, Xing, Guo, Ziwei, Zhang, Tingting, Fu, Yali, Zhang, Lingling, Wang, Xiangyi, Lin, Li, Liang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036564/
https://www.ncbi.nlm.nih.gov/pubmed/30013628
http://dx.doi.org/10.3892/ol.2018.8936
_version_ 1783338186664050688
author Ding, Xiaosheng
Li, Li
Tang, CHuanhao
Meng, Chao
Xu, Weiran
Wei, Xing
Guo, Ziwei
Zhang, Tingting
Fu, Yali
Zhang, Lingling
Wang, Xiangyi
Lin, Li
Liang, Jun
author_facet Ding, Xiaosheng
Li, Li
Tang, CHuanhao
Meng, Chao
Xu, Weiran
Wei, Xing
Guo, Ziwei
Zhang, Tingting
Fu, Yali
Zhang, Lingling
Wang, Xiangyi
Lin, Li
Liang, Jun
author_sort Ding, Xiaosheng
collection PubMed
description There is growing evidence that estrogen receptors (ER) are expressed in lung cancer cells, and are able to interact with the epidermal growth factor receptor (EGFR) signaling pathway. However, data on the association between cytoplasmic ER expression and the response to EGFR-tyrosine kinase inhibitors (TKI) treatment are limited. The aim of the present study was to investigate the associations between ERα/ERβ expression and EGFR mutational status and response to TKI treatment in metastatic lung adenocarcinoma. A retrospective study of 126 consecutive patients with lung adenocarcinoma who were diagnosed with stage IV disease and had received EGFR-TKI treatment was conducted. ER expression was detected by immunohistochemistry. EGFR and GTPase KRas (KRAS) mutational statuses were evaluated by denaturing high performance liquid chromatography and PCR-restriction fragment length polymorphism, respectively. In the overall cohort of 126 lung adenocarcinoma samples analyzed, ERα expression in the nucleus of tumor cells was identified in 17 (18.9%) patients, whereas ERβ expression was identified in the nucleus (22/126, 17.5%) and cytoplasm (17/126, 13.5%). The nuclear expression of ERβ was positively associated with the degree of tumor differentiation (P=0.010). EGFR-sensitizing mutations were significantly associated with improved objective response rates (ORR), disease control rates (DCR), median progression-free survival (mPFS) and median overall survival (mOS) (P<0.001; P<0.001; P=0.003; and P=0.026, respectively). Patients with cytoplasmic ERβ expression exhibited non-significant poorer ORR, DCR, mPFS and mOS compared with patients without cytoplasmic ERβ expression (P=0.082; P=0.106; P=0.084; and P=0.119, respectively). However, the significant decrease of ORR, DCR and mPFS was observed in patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations (P=0.030; P=0.009; and P=0.018, respectively) in comparison with the subgroup with EGFR sensitizing mutations but negative expression of cytoplasmic ERβ. A trend towards shorter mOS was also observed in patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations (P=0.071). No KRAS mutations were identified in patients with cytoplasmic ERβ expression. Subsequent to adjusting for sex, smoking status and EGFR mutation status, the Cox repression analysis indicated that cytoplasmic expression of ERβ was a negative independent predictor for mPFS in the whole patient cohort (HR=1.870; 95% confidence interval 1.058–3.305; P=0.031). Cytoplasmic ERβ expression was negatively correlated with the efficacy of EGFR-TKI treatment for metastatic lung adenocarcinoma, particularly for patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations. Cytoplasmic ERβ may be a promising marker to predict the outcome of EGFR-TKI treatment.
format Online
Article
Text
id pubmed-6036564
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-60365642018-07-16 Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma Ding, Xiaosheng Li, Li Tang, CHuanhao Meng, Chao Xu, Weiran Wei, Xing Guo, Ziwei Zhang, Tingting Fu, Yali Zhang, Lingling Wang, Xiangyi Lin, Li Liang, Jun Oncol Lett Articles There is growing evidence that estrogen receptors (ER) are expressed in lung cancer cells, and are able to interact with the epidermal growth factor receptor (EGFR) signaling pathway. However, data on the association between cytoplasmic ER expression and the response to EGFR-tyrosine kinase inhibitors (TKI) treatment are limited. The aim of the present study was to investigate the associations between ERα/ERβ expression and EGFR mutational status and response to TKI treatment in metastatic lung adenocarcinoma. A retrospective study of 126 consecutive patients with lung adenocarcinoma who were diagnosed with stage IV disease and had received EGFR-TKI treatment was conducted. ER expression was detected by immunohistochemistry. EGFR and GTPase KRas (KRAS) mutational statuses were evaluated by denaturing high performance liquid chromatography and PCR-restriction fragment length polymorphism, respectively. In the overall cohort of 126 lung adenocarcinoma samples analyzed, ERα expression in the nucleus of tumor cells was identified in 17 (18.9%) patients, whereas ERβ expression was identified in the nucleus (22/126, 17.5%) and cytoplasm (17/126, 13.5%). The nuclear expression of ERβ was positively associated with the degree of tumor differentiation (P=0.010). EGFR-sensitizing mutations were significantly associated with improved objective response rates (ORR), disease control rates (DCR), median progression-free survival (mPFS) and median overall survival (mOS) (P<0.001; P<0.001; P=0.003; and P=0.026, respectively). Patients with cytoplasmic ERβ expression exhibited non-significant poorer ORR, DCR, mPFS and mOS compared with patients without cytoplasmic ERβ expression (P=0.082; P=0.106; P=0.084; and P=0.119, respectively). However, the significant decrease of ORR, DCR and mPFS was observed in patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations (P=0.030; P=0.009; and P=0.018, respectively) in comparison with the subgroup with EGFR sensitizing mutations but negative expression of cytoplasmic ERβ. A trend towards shorter mOS was also observed in patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations (P=0.071). No KRAS mutations were identified in patients with cytoplasmic ERβ expression. Subsequent to adjusting for sex, smoking status and EGFR mutation status, the Cox repression analysis indicated that cytoplasmic expression of ERβ was a negative independent predictor for mPFS in the whole patient cohort (HR=1.870; 95% confidence interval 1.058–3.305; P=0.031). Cytoplasmic ERβ expression was negatively correlated with the efficacy of EGFR-TKI treatment for metastatic lung adenocarcinoma, particularly for patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations. Cytoplasmic ERβ may be a promising marker to predict the outcome of EGFR-TKI treatment. D.A. Spandidos 2018-08 2018-06-08 /pmc/articles/PMC6036564/ /pubmed/30013628 http://dx.doi.org/10.3892/ol.2018.8936 Text en Copyright: © Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Ding, Xiaosheng
Li, Li
Tang, CHuanhao
Meng, Chao
Xu, Weiran
Wei, Xing
Guo, Ziwei
Zhang, Tingting
Fu, Yali
Zhang, Lingling
Wang, Xiangyi
Lin, Li
Liang, Jun
Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma
title Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma
title_full Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma
title_fullStr Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma
title_full_unstemmed Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma
title_short Cytoplasmic expression of estrogen receptor β may predict poor outcome of EGFR-TKI therapy in metastatic lung adenocarcinoma
title_sort cytoplasmic expression of estrogen receptor β may predict poor outcome of egfr-tki therapy in metastatic lung adenocarcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036564/
https://www.ncbi.nlm.nih.gov/pubmed/30013628
http://dx.doi.org/10.3892/ol.2018.8936
work_keys_str_mv AT dingxiaosheng cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT lili cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT tangchuanhao cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT mengchao cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT xuweiran cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT weixing cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT guoziwei cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT zhangtingting cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT fuyali cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT zhanglingling cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT wangxiangyi cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT linli cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma
AT liangjun cytoplasmicexpressionofestrogenreceptorbmaypredictpooroutcomeofegfrtkitherapyinmetastaticlungadenocarcinoma