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

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

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

Authors:
- 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
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Affiliations: Department of Urology, Nara Medical University, Kashihara, Nara 634‑8522, Japan, Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara 634‑8522, Japan, Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara 634‑8522, Japan, Department of Urology, Nara Prefecture General Medical Center, Nara 630‑8581, Japan, Department of Urology, Nara City Hospital, Nara 630‑8305, Japan
Published online on: September 3, 2020 https://doi.org/10.3892/ol.2020.12052
Article Number: 190
Copyright: © Miyake et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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