Programmed Death-Ligand 1 Expression in Lung Cancer and Paired Brain Metastases-a Single-Center Study in 190 Patients

Alexandra Kündig; Philipp Zens; Christian Fung; Amina Scherz; Ferdinando Cerciello; Evelyn Herrmann; Ekin Ermis; Ralph A Schmid; Erik Vassella; Sabina Berezowska

doi:10.1016/j.jtocrr.2022.100413

Programmed Death-Ligand 1 Expression in Lung Cancer and Paired Brain Metastases-a Single-Center Study in 190 Patients

JTO Clin Res Rep. 2022 Sep 20;3(11):100413. doi: 10.1016/j.jtocrr.2022.100413. eCollection 2022 Nov.

Authors

Alexandra Kündig^{1

2}, Philipp Zens^{1

3}, Christian Fung^{4

5}, Amina Scherz⁶, Ferdinando Cerciello⁶, Evelyn Herrmann⁷, Ekin Ermis⁷, Ralph A Schmid⁸, Erik Vassella¹, Sabina Berezowska^{1

9}

Affiliations

¹ Institute of Pathology, University of Bern, Bern, Switzerland.
² Present Address: Department of Otorhinolaryngology-Head and Neck Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland.
³ Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
⁴ Department of Neurosurgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Present Address: Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg, Germany.
⁶ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁸ Division of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁹ Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Abstract

Introduction: Expression of programmed death-ligand 1 (PD-L1) is the only routinely used tissue biomarker for predicting response to programmed cell death protein 1/PD-L1 inhibitors. It is to date unclear whether PD-L1 expression is preserved in brain metastases (BMs).

Methods: In this single-center, retrospective study, we evaluated PD-L1 expression using the SP263 assay in consecutively resected BMs of lung carcinomas and paired primary tumors, diagnosed from 2000 to 2015, with correlation to clinicopathological and molecular tumor and patient characteristics.

Results: PD-L1 tumor proportional score (TPS) could be evaluated on whole tissue slides in 191 BMs and 84 paired primary lung carcinomas. PD-L1 TPS was less than 1% in 113 of 191 (59.2%), 1% to 49% in 34 of 191 (17.8%), and greater than or equal to 50% in 44 of 191 (23.0%) BMs. TPS was concordant between BMs and paired primary lung carcinomas in most cases, with discordance regarding the clinically relevant cutoffs at 1% and 50% in 18 of 84 patients (21.4%). Four of 18 discordant cases had no shared mutations between the primary lung carcinoma and BM. Intratumoral heterogeneity, as assessed using tissue microarray cores, was only significant at the primary site (p _{Wilcoxon signed rank} = 0.002) with higher PD-L1 TPS at the infiltration front (mean = 40.4%, interquartile range: 0%-90%). Neither TPS greater than or equal to 1% nor TPS greater than or equal to 50% nor discordance between the primary lung carcinoma and BMs had prognostic significance regarding overall survival or BM-specific overall survival.

Conclusions: PD-L1 expression was mostly concordant between primary lung carcinoma and its BM and between resections of BM and stereotactic biopsies, mirrored by tissue microarray cores. Differences in PD-L1 TPS existed primarily in cases with TPS greater than 10%, for which also human assessment tends to be most error prone.

Keywords: Brain metastasis; Immune checkpoint inhibitors; Lung cancer; NSCLC; PD-L1.