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Association between PD-L1 expression and driver gene mutations in non-small cell lung cancer patients: correlation with clinical data

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Abstract

Lung cancer is the leading cause of cancer death worldwide. Recently, promising therapies have emerged based on PD-1/PD-L1 immune checkpoint inhibitors, which have been approved even as frontline treatment for patients with non-small cell lung cancer (NSCLC). We examined the association between PD-L1 expression and clinicopathological parameters as well as overall survival in 220 NSCLC patients. PD-L1 expression was estimated by immunohistochemistry using 22C3 PharmDx Dako assay and was defined as high, if TPS was ≥ 50%, low, if TPS was 1%–49%, and absent, if TPS was < 1%. EGFR mutations were detected by COBAS while KRAS and BRAF mutations by pyrosequencing. ROS1 and ALK rearrangements were estimated by immunohistochemistry with positive cases being confirmed by CISH and FISH, respectively. Data analysis was performed using SPSS v25.0. PD-L1 expression was positively correlated with KRAS mutations. Anti-PD-1 therapy (pembrolizumab) prolonged overall survival compared to any other treatment. This effect was more pronounced in KRAS-mutated cases compared to KRAS wild-type ones. Patients with positive PD-L1 expression – high or low – who had been treated with pembrolizumab, showed significant survival benefit compared to positive or negative PD-L1 expressors who did not receive immunotherapy. In multivariate analysis, PD-L1 status, stage and pembrolizumab treatment were independent variables for overall survival. PD-L1 expression (TPS ≥ 1%) by itself emerged as a poor prognostic factor, while treatment with pembrolizumab prolonged overall survival. KRAS mutations may affect tumour microenvironment and patient’s response to immunotherapy. Immune checkpoint inhibitors could represent an alternative therapeutic option particularly for KRAS-mutated NSCLC patients. Further investigation into this notion is warranted in order to validate this observation.

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  1. Penelope Korkolopoulou and Angelica A. Saetta have equally contributed as senior authors to this manuscript

Authors and Affiliations

  1. First Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece

    Eleni A. Karatrasoglou, Ilenia Chatziandreou, Stratigoula Sakellariou, Nikolaos Kavantzas, Andreas C. Lazaris, Penelope Korkolopoulou & Angelica A. Saetta

  2. Agii Anargiri General Oncological Hospital of Kifissia, Kifisia, Greece

    Konstantinos Stamopoulos

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Contributions

Eleni A. Karatrasoglou: study design, data analysis, paper drafting

Ilenia Chatziandreou: data analysis, performed experiments, paper drafting

Stratigoula Sakellariou: study design, histopathological analysis, paper drafting

Konstantinos Stamopoulos: clinical data collection and analysis, paper drafting

Nikolaos Kavantzas: paper critical revision

Andreas C. Lazaris: paper critical revision

Penelope Korkolopoulou: study design, histopathological analysis, paper critical revision, paper drafting

Angelica A. Saetta: study design, performed experiments, paper critical revision, paper drafting

All authors gave final approval of the final version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Eleni A. Karatrasoglou, Ilenia Chatziandreou, Stratigoula Sakellariou and Konstantinos Stamopoulos have equally contributed to this manuscript.

Penelope Korkolopoulou and Angelica A. Saetta have equally contributed as senior authors to this manuscript.

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Correspondence to Eleni A. Karatrasoglou.

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Karatrasoglou, E.A., Chatziandreou, I., Sakellariou, S. et al. Association between PD-L1 expression and driver gene mutations in non-small cell lung cancer patients: correlation with clinical data. Virchows Arch 477, 207–217 (2020). https://doi.org/10.1007/s00428-020-02756-1

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