Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer

Aaron Mansfield, Stephen J. Murphy, Tobias D Peikert, Eunhee S. Yi, George Vasmatzis, Dennis A Wigle, Marie Christine Aubry

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Purpose: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers. Experimental Design: PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis. Results: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (k = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (k = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (k = 0.73). Conclusions: The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis.

Original languageEnglish (US)
Pages (from-to)2177-2182
Number of pages6
JournalClinical Cancer Research
Volume22
Issue number9
DOIs
StatePublished - May 1 2016

Fingerprint

Lung Neoplasms
Cell Death
Ligands
Neoplasms
Selection Bias
Immunotherapy
Research Design
Neoplasm Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer. / Mansfield, Aaron; Murphy, Stephen J.; Peikert, Tobias D; Yi, Eunhee S.; Vasmatzis, George; Wigle, Dennis A; Aubry, Marie Christine.

In: Clinical Cancer Research, Vol. 22, No. 9, 01.05.2016, p. 2177-2182.

Research output: Contribution to journalArticle

@article{88e5da4314034cb8b78495141df5245b,
title = "Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer",
abstract = "Purpose: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers. Experimental Design: PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis. Results: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (k = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (k = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (k = 0.73). Conclusions: The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis.",
author = "Aaron Mansfield and Murphy, {Stephen J.} and Peikert, {Tobias D} and Yi, {Eunhee S.} and George Vasmatzis and Wigle, {Dennis A} and Aubry, {Marie Christine}",
year = "2016",
month = "5",
day = "1",
doi = "10.1158/1078-0432.CCR-15-2246",
language = "English (US)",
volume = "22",
pages = "2177--2182",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer

AU - Mansfield, Aaron

AU - Murphy, Stephen J.

AU - Peikert, Tobias D

AU - Yi, Eunhee S.

AU - Vasmatzis, George

AU - Wigle, Dennis A

AU - Aubry, Marie Christine

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Purpose: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers. Experimental Design: PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis. Results: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (k = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (k = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (k = 0.73). Conclusions: The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis.

AB - Purpose: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers. Experimental Design: PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis. Results: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (k = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (k = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (k = 0.73). Conclusions: The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis.

UR - http://www.scopus.com/inward/record.url?scp=84968895056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84968895056&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-15-2246

DO - 10.1158/1078-0432.CCR-15-2246

M3 - Article

VL - 22

SP - 2177

EP - 2182

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 9

ER -