Clinicopathological characteristics of POLE mutation in patients with non-small-cell lung cancer.

Autor: Song Z; Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China. Electronic address: songzb@zjcc.org.cn., Cheng G; Department of Pathology, Zhejiang Cancer Hospital, Hangzhou 310022, China., Xu C; Department of Pathology, Fujian Cancer Hospital, Hangzhou 350014, China., Wang W; Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China., Shao Y; Geneseeq Biotechnology Inc., Nanjing 210061, China., Zhang Y; Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China. Electronic address: zjzlyy16@163.com.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2018 Apr; Vol. 118, pp. 57-61. Date of Electronic Publication: 2018 Feb 06.
DOI: 10.1016/j.lungcan.2018.02.004
Abstrakt: Background: Mutations in polymerase ε (POLE), a DNA polymerase involved in DNA replication and repair, have been investigated in endometrial cancers and response to programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) immunotherapy. However, the frequency of POLE gene mutation in patients with non-small cell lung cancer (NSCLC) has not been reported.
Materials and Methods: We assessed POLE mutation in 319 patients with NSCLC by next-generation sequencing (NGS) of 416 cancer-associated genes. Expression of PD-L1, DNA mismatch repair proteins (MMR), and the abundance of CD8-positive tumor infiltrating lymphocytes (TILs) were assayed by immunohistochemistry. Progression-free survival (PFS) was evaluated using the Kaplan-Meier method and compared among groups using log-rank tests.
Results: Nine of the 319 patients (2.8%) harbored POLE mutation. All nine had adenocarcinomas. The median tumor mutational burdens (TMBs) were 12.2/Mb and 7.8/Mb in patients with and without POLE mutation, respectively (P = 0.026). PD-L1, MMR (including MSH2, MSH6, MLH1 and PMS2), and CD8-positive TILs were evaluated in all nine patients. No microsatellite instability was detected, but seven patients had high levels of CD8-positive TILs and five demonstrated PD-L1 staining >25%. One patient receiving the PD-L1 antibody atezolizumab demonstrated a partial response, with a PFS of >8 months.
Conclusion: POLE mutation represents an uncommon phenotype in NSCLC. TMB, PD-L1 expression, and CD8-positive TILs were all higher in patients with mutant compared with wild-type POLE. POLE mutation may thus represent a candidate biomarker for response to immunotherapy in patients with NSCLC.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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