Research Papers:

Programmed death-ligand 1 expression according to epidermal growth factor receptor mutation status in pretreated non-small cell lung cancer

Akito Hata _, Nobuyuki Katakami, Shigeki Nanjo, Chiyuki Okuda, Reiko Kaji, Katsuhiro Masago, Shiro Fujita, Hiroshi Yoshida, Kota Zama, Yukihiro Imai and Yukio Hirata

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Oncotarget. 2017; 8:113807-113816. https://doi.org/10.18632/oncotarget.22837

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Akito Hata1, Nobuyuki Katakami1, Shigeki Nanjo1, Chiyuki Okuda1, Reiko Kaji1, Katsuhiro Masago1, Shiro Fujita1, Hiroshi Yoshida2, Kota Zama2, Yukihiro Imai3 and Yukio Hirata1

1Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital, Kobe, Japan

2Department of Contract Research for Clinical Pathology, GeneticLab Co. Ltd., Sapporo, Japan

3Department of Clinical Pathology, Kobe City Medical Center, General Hospital, Kobe, Japan

Correspondence to:

Akito Hata, email: [email protected]

Keywords: PD-L1; EGFR mutation; non-small cell lung cancer; PD-L1 IHC; PD-L1 antibody

Received: April 12, 2017    Accepted: November 11, 2017    Published: December 01, 2017


Background: Current clinical trials have suggested poorer efficacies of anti-programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immunotherapies for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, implying lower PD-L1 expression in EGFR-mutant NSCLC than in EGFR-wild type.

Methods: We retrospectively analyzed correlation between PD-L1 expression and EGFR status in clinical samples of pretreated NSCLC. PD-L1 immunohistochemistry was performed using the 28-8 anti-PD-L1 antibody for tumor cell membrane staining. H-score was adopted to evaluate both percentage and intensity. We investigated H-scores ≥1, ≥5, and ≥10 as PD-L1+ cut-offs. H-score ≥10 was defined as strong PD-L1+.

Results: We investigated 96 available histologic samples in 77 pretreated patients with NSCLC. Median H-score in EGFR-mutant samples (n=65) was 3 (range, 0-150), whereas EGFR-wild-type (n=31) was 8 (range, 0-134) (p=0.0075). Using H-scores ≥1, ≥5, and ≥10 cut-offs, incidence of PD-L1+ in EGFR-mutant vs. EGFR-wild-type samples were: 85% (55/65) vs. 94% (29/31) (p=0.2159); 42% (27/65) vs. 74% (23/31) (p=0.0027); and 22% (14/65) vs. 48% (15/31) (p=0.0074), respectively. Patient-oriented (n=77) univariate analysis for strong PD-L1+ found age of sample (p=0.0226) and EGFR mutation status (p=0.0490) as significant factors. Multivariate analysis identified EGFR mutation status as the only significant factor (p=0.0121, odds ratio 2.99) for strong PD-L1+. H-scores of PD-L1 expression varied in all 11 cases receiving multiple rebiopsies, and categories of positivity migrated in 10 (91%) of 11 patients.

Conclusions: PD-L1 expression was significantly lower in EGFR-mutant NSCLC samples than in EGFR wild-type samples. Its expression could be dynamic and affected by age of sample.

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