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Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN expression as a means for tissue quality screening

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Abstract

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.

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Abbreviations

CI:

Confidence interval

HR:

Hazard ratio

IC:

Immune cell

NSCLC:

Non-small cell lung cancer

PTEN:

Phosphatase and tensin homolog

RFS:

Recurrence-free survival

TC:

Tumor cell

TMA:

Tissue microarray

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Acknowledgements

We thank Robert Clarke (Oncology Biomarker Development, Genentech Inc., Basel, Switzerland) for his project management support to this study and Ventana Medical Systems, Inc. (Tucson, AZ, USA) for making the PD-L1 IHC assay available for this study.

Author information

Authors and Affiliations

Authors

Contributions

Conception and design of study: YW, GC, XZ, JH, and DS. Acquisition of data: XC, CS, ZX, JG, JY, XY, and HK. Analysis and/or interpretation of data: GC, XZ, XC, CS, HD, SL, XX, YZ, and MC. Drafting the manuscript: GC, XZ, XC, JG, and CS. Revising the manuscript critically for important intellectual content: ZX, JY, XY, HD, SL, XX, YZ, MC, HK, JH, AK, DS, and YW. Approval of the version of the manuscript to be published (the names of all authors listed): XZ, XC, CS, ZX, JG, JY, XY, HD, SL, XX, YZ, MC, HK, JH, AK, DS, GC, and YW.

Corresponding authors

Correspondence to Gang Cheng or Yi-long Wu.

Ethics declarations

Funding

This study was supported by Genentech Inc., a member of the Roche Group. This work was also supported by Special Fund of Public Interest from National Health and Family Control Committee (Grant No. 201402031), Key Lab System Project of Guangdong S&T Department (Grant No. 2012A061400006), The Guangdong Provincial Applied S&T Research and Development Program (Grant No. 2016B020237006), General Research Project of Guangzhou Science and Technology Bureau (Grant No. 201607010391), The National Key Research and Development Program of China (Grant No. 2016YFC1303800), and Public Welfare and Capacity Establishment Program of Guangdong Science and Technology Department (Grant No. 2014A020212225).

Conflict of interest

Chun Sun, Hang-jun Dai, Su-chun Li, and Yun-xia Zuo are employees of F. Hoffmann-La Roche/Genentech Inc. Xu Cao, Jian-jun Guo, Xin-ran Xu, Meng Chen, Hartmut Koeppen, Jing He, Astrid Kiermaier, David Shames, and Gang Cheng are employees of F. Hoffmann-La Roche/Genentech Inc. and hold stocks of F. Hoffmann-La Roche. All the other authors declare no conflict of interest.

Ethical approval and ethical standards

This study was approved by the institutional review board of Guangdong General Hospital in Guangzhou, China according to the Helsinki declaration.

Informed consent

The acquisition of written informed consent was waived by the institutional review board of Guangdong General Hospital in Guangzhou, China with the condition that all samples must be anonymized during the study.

Additional information

Results in this paper have been published before as a poster titled “Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN IHC as a means for sample quality screening” in ESMO Asia 2016, December 16–19, 2016, Singapore [1].

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Zhang, Xc., Cao, X., Sun, C. et al. Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN expression as a means for tissue quality screening. Cancer Immunol Immunother 67, 471–481 (2018). https://doi.org/10.1007/s00262-017-2098-4

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