Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer

K. Azuma, keiichi ota, A. Kawahara, S. Hattori, Eiji Iwama, Taishi Harada, K. Matsumoto, K. Takayama, S. Takamori, M. Kage, T. Hoshino, Yoichi Nakanishi, Isamu Okamoto

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Recent clinical trials have shown that immune-checkpoint blockade yields a clinical response in a subset of individuals with advanced nonsmall-cell lung cancer (NSCLC). We examined whether the expression of programmed death-ligand 1 (PD-L1) is related to clinicopathologic or prognostic factors in patients with surgically resected NSCLC.

PATIENTS AND METHODS: The expression of PD-L1 was evaluated by immunohistochemical analysis in 164 specimens of surgically resected NSCLC. Cell surface expression of PD-L1 in NSCLC cell lines was quantified by flow cytometry.

RESULTS: Expression of PD-L1 in tumor specimens was significantly higher for women than for men, for never smokers than for smokers, and for patients with adenocarcinoma than for those with squamous cell carcinoma. Multivariate analysis revealed that the presence of epidermal growth factor receptor gene (EGFR) mutations and adenocarcinoma histology were significantly associated with increased PD-L1 expression in a manner independent of other factors. Cell surface expression of PD-L1 was also significantly higher in NSCLC cell lines positive for activating EGFR mutations than in those with wild-type EGFR. The EGFR inhibitor erlotinib downregulated PD-L1 expression in the former cell lines but not in the latter, suggesting that PD-L1 expression is increased by EGFR signaling conferred by activating EGFR mutations. A high level of PD-L1 expression in resected tumor tissue was associated with a significantly shorter overall survival for NSCLC patients.

CONCLUSIONS: High expression of PD-L1 was associated with the presence of EGFR mutations in surgically resected NSCLC and was an independent negative prognostic factor for this disease.

Original languageEnglish
Pages (from-to)1935-1940
Number of pages6
JournalAnnals of oncology : official journal of the European Society for Medical Oncology / ESMO
Volume25
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

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erbB-1 Genes
Non-Small Cell Lung Carcinoma
Ligands
Mutation
Cell Line
Adenocarcinoma
Squamous Cell Carcinoma
Neoplasms
Histology
Flow Cytometry
Down-Regulation
Multivariate Analysis
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. / Azuma, K.; ota, keiichi; Kawahara, A.; Hattori, S.; Iwama, Eiji; Harada, Taishi; Matsumoto, K.; Takayama, K.; Takamori, S.; Kage, M.; Hoshino, T.; Nakanishi, Yoichi; Okamoto, Isamu.

In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, Vol. 25, No. 10, 01.10.2014, p. 1935-1940.

Research output: Contribution to journalArticle

Azuma, K. ; ota, keiichi ; Kawahara, A. ; Hattori, S. ; Iwama, Eiji ; Harada, Taishi ; Matsumoto, K. ; Takayama, K. ; Takamori, S. ; Kage, M. ; Hoshino, T. ; Nakanishi, Yoichi ; Okamoto, Isamu. / Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2014 ; Vol. 25, No. 10. pp. 1935-1940.
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AU - Azuma, K.

AU - ota, keiichi

AU - Kawahara, A.

AU - Hattori, S.

AU - Iwama, Eiji

AU - Harada, Taishi

AU - Matsumoto, K.

AU - Takayama, K.

AU - Takamori, S.

AU - Kage, M.

AU - Hoshino, T.

AU - Nakanishi, Yoichi

AU - Okamoto, Isamu

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N2 - BACKGROUND: Recent clinical trials have shown that immune-checkpoint blockade yields a clinical response in a subset of individuals with advanced nonsmall-cell lung cancer (NSCLC). We examined whether the expression of programmed death-ligand 1 (PD-L1) is related to clinicopathologic or prognostic factors in patients with surgically resected NSCLC.PATIENTS AND METHODS: The expression of PD-L1 was evaluated by immunohistochemical analysis in 164 specimens of surgically resected NSCLC. Cell surface expression of PD-L1 in NSCLC cell lines was quantified by flow cytometry.RESULTS: Expression of PD-L1 in tumor specimens was significantly higher for women than for men, for never smokers than for smokers, and for patients with adenocarcinoma than for those with squamous cell carcinoma. Multivariate analysis revealed that the presence of epidermal growth factor receptor gene (EGFR) mutations and adenocarcinoma histology were significantly associated with increased PD-L1 expression in a manner independent of other factors. Cell surface expression of PD-L1 was also significantly higher in NSCLC cell lines positive for activating EGFR mutations than in those with wild-type EGFR. The EGFR inhibitor erlotinib downregulated PD-L1 expression in the former cell lines but not in the latter, suggesting that PD-L1 expression is increased by EGFR signaling conferred by activating EGFR mutations. A high level of PD-L1 expression in resected tumor tissue was associated with a significantly shorter overall survival for NSCLC patients.CONCLUSIONS: High expression of PD-L1 was associated with the presence of EGFR mutations in surgically resected NSCLC and was an independent negative prognostic factor for this disease.

AB - BACKGROUND: Recent clinical trials have shown that immune-checkpoint blockade yields a clinical response in a subset of individuals with advanced nonsmall-cell lung cancer (NSCLC). We examined whether the expression of programmed death-ligand 1 (PD-L1) is related to clinicopathologic or prognostic factors in patients with surgically resected NSCLC.PATIENTS AND METHODS: The expression of PD-L1 was evaluated by immunohistochemical analysis in 164 specimens of surgically resected NSCLC. Cell surface expression of PD-L1 in NSCLC cell lines was quantified by flow cytometry.RESULTS: Expression of PD-L1 in tumor specimens was significantly higher for women than for men, for never smokers than for smokers, and for patients with adenocarcinoma than for those with squamous cell carcinoma. Multivariate analysis revealed that the presence of epidermal growth factor receptor gene (EGFR) mutations and adenocarcinoma histology were significantly associated with increased PD-L1 expression in a manner independent of other factors. Cell surface expression of PD-L1 was also significantly higher in NSCLC cell lines positive for activating EGFR mutations than in those with wild-type EGFR. The EGFR inhibitor erlotinib downregulated PD-L1 expression in the former cell lines but not in the latter, suggesting that PD-L1 expression is increased by EGFR signaling conferred by activating EGFR mutations. A high level of PD-L1 expression in resected tumor tissue was associated with a significantly shorter overall survival for NSCLC patients.CONCLUSIONS: High expression of PD-L1 was associated with the presence of EGFR mutations in surgically resected NSCLC and was an independent negative prognostic factor for this disease.

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