Integrative assessment of clinicopathological parameters and the expression of PD-L1, PD-L2 and PD-1 in tumor cells of retroperitoneal sarcoma

Makito Miyake; Yuki Oda; Nobutaka Nishimura; Yosuke Morizawa; Sayuri Ohnishi; Kinta Hatakeyama; Tomomi Fujii; Shunta Hori; Daisuke Gotoh; Yasushi Nakai; Satoshi Anai; Kazumasa Torimoto; Shinji Tsukamoto; Hiromasa Fujii; Akira Kido; Kanya Honoki; Yoshiaki Matsumura; Eijiro Okajima; Nobumichi Tanaka; Kiyohide Fujimoto

doi:10.3892/ol.2020.12052

Integrative assessment of clinicopathological parameters and the expression of PD-L1, PD-L2 and PD-1 in tumor cells of retroperitoneal sarcoma

Oncol Lett. 2020 Nov;20(5):190. doi: 10.3892/ol.2020.12052. Epub 2020 Sep 3.

Authors

Makito Miyake¹, Yuki Oda¹, Nobutaka Nishimura¹, Yosuke Morizawa¹, Sayuri Ohnishi¹, Kinta Hatakeyama², Tomomi Fujii², Shunta Hori¹, Daisuke Gotoh¹, Yasushi Nakai¹, Satoshi Anai¹, Kazumasa Torimoto¹, Shinji Tsukamoto³, Hiromasa Fujii³, Akira Kido³, Kanya Honoki³, Yoshiaki Matsumura⁴, Eijiro Okajima⁵, Nobumichi Tanaka^{1

6}, Kiyohide Fujimoto¹

Affiliations

¹ Department of Urology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
² Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
³ Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
⁴ Department of Urology, Nara Prefecture General Medical Center, Nara 630-8581, Japan.
⁵ Department of Urology, Nara City Hospital, Nara 630-8305, Japan.
⁶ Department of Prostate Brachytherapy, Nara Medical University, Kashihara, Nara 634-8522, Japan.

Abstract

Evidence is limited regarding the immunologic profile and immune microenvironment of soft tissue sarcoma subtypes. The aim of the present study was to describe the clinical significance and prognostic implications of PD-L1, PD-L2, and PD-1 in patients with retroperitoneal sarcoma (RSar). In this retrospective, multicenter, collaborative study, medical charts were reviewed and the immunohistochemical staining results of resected tissue specimens from 51 patients with RSar were examined. Immunohistochemical staining was performed with primary antibodies against PD-L1, PD-L2, PD-1, and Ki-67. The correlations between the baseline clinical parameters and expression levels of the four molecules in sarcoma cells were evaluated, and their prognostic values after tumor resection were assessed. Dedifferentiated liposarcoma (41%), leiomyosarcoma (20%), and undifferentiated pleomorphic sarcoma (16%) were the three major types identified. Dedifferentiated liposarcoma and leiomyosarcoma showed higher levels of PD-L1 expression than did other sarcomas. The Spearman correlation analysis revealed that baseline serum lactate dehydrogenase levels were moderately and positively correlated with PD-L1 (P=0.02, r=0.41) and PD-L2 (P=0.006, r=0.47) expression. The median recurrence-free and disease-specific survival was 58 and 16 months, respectively, during the 29-month median follow-up after surgery. On univariate analysis, a higher expression level of PD-1 was associated with a higher risk of recurrence, whereas multivariate analyses revealed that independent predictors of recurrence-free and disease-specific survival indicated a high expression of Ki-67 (P=0.03; hazard ratio, 2.29 vs. low expression) and prognostic stage IIIB (P=0.04; hazard ratio, 5.11 vs. stage I-II), respectively. Findings of the current study provide novel insights about the prognostic value of PD-L1, PD-L2, and PD-1 expression in RSar. Serum lactate dehydrogenase levels constitute a potential predictor of PD-L1 and PD-L2 expression levels in RSar. Further investigations are needed to determine the immunologic landscape of RSar and provide a foundation for therapeutic intervention using immune checkpoint inhibitors.

Keywords: Ki-67; leiomyosarcoma; liposarcoma; prognosis; program cell death ligand-1; program cell death ligand-2; programmed cell death-1; retroperitoneal sarcoma; surgery; undifferentiated pleomorphic sarcoma.