AUTHOR=Song Joon Seon , Kim Deokhoon , Kwon Ji Hyun , Kim Hyeong Ryul , Choi Chang-Min , Jang Se Jin 

TITLE=Clinicopathologic Significance and Immunogenomic Analysis of Programmed Death-Ligand 1 (PD-L1) and Programmed Death 1 (PD-1) Expression in Thymic Epithelial Tumors

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01055

DOI=10.3389/fonc.2019.01055

ISSN=2234-943X

ABSTRACT=<p><bold>Objectives:</bold> Thymic epithelial tumors (TETs) are rare malignant tumors that exhibit heterogeneous histology and clinical behavior. As immune check point inhibitors, drugs targeting anti-programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown remarkable results against many cancers; thus, the importance of PD-1/PD-L1 immunohistochemistry as a predictive or prognostic biomarker has grown. However, limited data on PD-L1 and PD-1 expression in TETs have been reported; moreover, these results have been variable. Here, we examined the expression of PD-1/PD-L1 proteins in TETs and analyzed the clinicopathologic significance of this expression.</p><p><bold>Patients and Methods:</bold> A tissue microarray was constructed using 368 samples of 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 with clinicopathologic characteristics were analyzed. PD-L1<sup>high</sup> was designated as ≥50% of tumor proportion score; PD-1<sup>high</sup> and CD8<sup>high</sup> were defined as ≥5% and 1% of tumoral immune cells, respectively.</p><p><bold>Results:</bold> 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 of intra-/peritumoral T cells was identified in 53.6% (194/362) of TETs and CD8 positivity was identified in 11% (7/60, ≥1%) of TC. Of the 362 patients, 141 (39.0%) exhibited high PD-L1 expression (PD-L1<sup>high</sup>). The PD-L1<sup>high</sup> thymoma group was correlated with high Masaoka-Koga stage (<italic>p</italic> &lt; 0.001), type B3 histology (<italic>p</italic> &lt; 0.001), and myasthenia gravis (<italic>p</italic> &lt; 0.001). This group exhibited poor overall survival (OS, <italic>p</italic> = 0.003, log-rank) and worse disease-free survival (DFS, <italic>p</italic> = 0.042, log-rank). No survival differences were detected between PD-L1<sup>high</sup> and PD-L1<sup>low</sup> groups in TC. Additionally, there was no correlation between PD-1 expression and survival in patients with TETs. Multivariate analysis revealed that PD-L1<sup>high</sup> expression was an independent poor prognostic factor (<italic>p</italic> = 0.047, HR 2.087, 95% CI, 1.009–4.318) in thymomas.</p><p><bold>Conclusions:</bold> To our knowledge, this is the largest study on TETs published in English literature. This study provides useful information regarding the prognosis of and potential therapeutic options for patients with TETs.</p>