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Mismatch repair status and high expression of PD-L1 in nasopharyngeal carcinoma

Authors Zhao L, Liao X, Hong G, Zhuang Y, Fu K, Chen P, Wang Y, Chen H, Lin Q

Received 8 November 2018

Accepted for publication 28 January 2019

Published 19 February 2019 Volume 2019:11 Pages 1631—1640

DOI https://doi.org/10.2147/CMAR.S193878

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 5

Editor who approved publication: Dr Ahmet Emre Eskazan


Liang Zhao,1,* Xiyi Liao,1,* Ganji Hong,1 Yanzhen Zhuang,2 Kaili Fu,1 Peiqiong Chen,2 Yuhuan Wang,2 Haojun Chen,3 Qin Lin1

1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 2Department of Pathology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 3Department of Nuclear Medicine & Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China

*These authors contributed equally to this work

Purpose: To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment.
Patients and methods: A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining.
Results: Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I–III accounted for 35 (49.3%) cases, while stage IVa–IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage (P=0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein–Barr virus DNA load (P=0.021), N stage (P=0.009), M stage (P=0.014), and clinical stage (P=0.001).
Conclusion: dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted.

Keywords: immunotherapy, biomarker, microsatellite instability, PD-L1, tumor-infiltrating immune cells
 

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