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Frontiers in Oncology, 2019. 9, 1055-, DOI: https://doi.org/10.3389/fonc.2019.01055
Clinicopathologic Significance and Immunogenomic Analysis of Programmed Death-Ligand 1 (PD-L1) and Programmed Death 1 (PD-1) Expression in Thymic Epithelial Tumors
Joon Seon Song, Deokhoon Kim;Ji Hyun Kwon;Hyeong Ryul Kim;Chang-Min Choi;Se Jin Jang
Objectives: Thymic epithelial tumors (TETs) are rare malignant tumors that exhibitheterogeneous histology and clinical behavior. As immune check point inhibitors, drugstargeting anti-programmed cell death protein 1 (PD-1) and programmed death-ligand1 (PD-L1) have shown remarkable results against many cancers; thus, the importanceof PD-1/PD-L1 immunohistochemistry as a predictive or prognostic biomarker hasgrown. However, limited data on PD-L1 and PD-1 expression in TETs have beenreported; moreover, these results have been variable. Here, we examined the expressionof PD-1/PD-L1 proteins in TETs and analyzed the clinicopathologic significance ofthis expression.
Patients and Methods: A tissue microarray was constructed using 368 samplesof TETs, each in triplicate. Immunohistochemistry for PD-L1 (SP263 assay) and PD-1 in TETs and CD8 in thymic carcinoma (TC) was performed; next, correlations withclinicopathologic characteristics were analyzed. PD-L1high was designated as 50% oftumor proportion score; PD-1high and CD8high were defined as 5% and 1% of tumoralimmune cells, respectively.
Results: The cohort consisted of 308 patients with thymomas and 60 patients with TC.PD-L1 positivity was identified in 90.6% (328/362, 1%) of TETs, PD-1 expression ofintra-/peritumoral T cells was identified in 53.6% (194/362) of TETs and CD8 positivitywas identified in 11% (7/60, 1%) of TC. Of the 362 patients, 141 (39.0%) exhibitedhigh PD-L1 expression (PD-L1high). The PD-L1high thymoma group was correlated withhigh Masaoka-Koga stage (p < 0.001), type B3 histology (p < 0.001), and myastheniagravis (p < 0.001). This group exhibited poor overall survival (OS, p = 0.003, log-rank)and worse disease-free survival (DFS, p = 0.042, log-rank). No survival differences weredetected between PD-L1high and PD-L1low groups in TC. Additionally, there was noSong et al. PD-L1/PD-1 Expression in Thymic Epithelial Tumorcorrelation between PD-1 expression and survival in patients with TETs. Multivariateanalysis revealed that PD-L1high expression was an independent poor prognostic factor(p = 0.047, HR 2.087, 95% CI, 1.009–4.318) in thymomas.
Conclusions: To our knowledge, this is the largest study on TETs published in Englishliterature. This study provides useful information regarding the prognosis of and potentialtherapeutic options for patients with TETs.
- DOI: https://doi.org/10.3389/fonc.2019.01055
- ISBN or ISSN: 2234-943X
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.