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J Thorac Oncol. 2018 May;13(5):636-648. doi: 10.1016/j.jtho.2018.01.008. Epub 2018 Jan 31.

Association of PD-L1 Expression with Tumor-Infiltrating Immune Cells and Mutation Burden in High-Grade Neuroendocrine Carcinoma of the Lung.

Author information

1
Division of Oncology/Hematology, Department of Internal Medicine, Myongji Hospital, Goyang-si Gyeonggi-do, Republic of Korea.
2
Department of Pathology, Korea University Medical Center, Anam Hospital, Seoul, Republic of Korea.
3
Department of Pathology, Asan Medical Center, Seoul, Republic of Korea.
4
Theragen Etex Bio Institute, Suwon-si Gyeonggi-do, Republic of Korea.
5
Center for Uterine Cancer, Department of Pathology, Research Institute and Hospital, National Cancer Center, Goyang-si Gyeonggi-do, Republic of Korea.
6
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si Gyeonggi-do, Republic of Korea.
7
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si Gyeonggi-do, Republic of Korea. Electronic address: jymama@ncc.re.kr.

Abstract

INTRODUCTION:

The immune microenvironment of high-grade neuroendocrine carcinoma of the lung, including programmed death ligand 1 (PD-L1) expression, has not been well characterized.

METHODS:

On the basis of immunohistochemistry (IHC) results, PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) was scored as follows: TC0 and IC0 were defined as PD-L1 expression less than 1%, TC1 and IC1 as at least 1% but less than 10%, TC2 and IC2 as 10% or more but less than 50%, and TC3 and IC3 as 50% or more. Phosphatase and tensin homolog (PTEN) IHC was scored as either lost or retained expression. The Ion AmpliSeq Comprehensive Cancer Panel (ThermoFisher Scientific, Waltham, MA) was used to identify mutations in all coding exons of 409 cancer-related genes.

RESULTS:

A total of 192 patients with large cell neuroendocrine carcinoma (LCNEC) (n = 72) and SCLC (n = 120) were studied. The prevalence of PD-L1 expression on TCs was 15.1% (29 of 192). IC infiltration and PD-L1 expression on ICs were observed in 34.4% of patients (66 of 192) and 31.3% of patients (60 of 192), respectively. The prevalence of IC infiltration and PD-L1 expression on IC were more strongly correlated with LCNEC than with SCLC (57.6% versus 23.3%, p < 0.01; 45.8% versus 22.5%, p < 0.01) and high nonsynonymous mutations (p = 0.05 and .04). PTEN loss was found in 9.5% of patients (18 of 189) and showed no correlation with PD-L1 expression. Progression-free survival was better in patients with IC infiltration than in those without IC infiltration (median 11.3 versus 6.8 months [p < 0.01]) and in patients with PD-L1 expression of IC1/2/3 than in those with expression of IC0 (median 11.3 versus 7.0 months [p = 0.03]).

CONCLUSION:

These findings suggest that the PD-1/PD-L1 pathway is activated in the microenvironment of pulmonary high-grade neuroendocrine carcinoma and correlated with a higher mutation burden.

KEYWORDS:

Large cell neuroendocrine lung cancer; Mutation burden; Programmed cell death ligand 1; Small cell lung cancer; Tumor-infiltrating immune cell

PMID:
29378266
DOI:
10.1016/j.jtho.2018.01.008
[Indexed for MEDLINE]

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