B7-H3 expression in upper tract urothelial carcinoma associates with adverse clinicopathological features and poor survival

Yuichi Koyama; Teppei Morikawa; Yu Miyama; Jimpei Miyakawa; Taketo Kawai; Haruki Kume; Motoji Sawabe; Tetsuo Ushiku

doi:10.1016/j.prp.2020.153219

B7-H3 expression in upper tract urothelial carcinoma associates with adverse clinicopathological features and poor survival

Pathol Res Pract. 2020 Dec;216(12):153219. doi: 10.1016/j.prp.2020.153219. Epub 2020 Sep 21.

Authors

Yuichi Koyama¹, Teppei Morikawa², Yu Miyama³, Jimpei Miyakawa⁴, Taketo Kawai⁴, Haruki Kume⁴, Motoji Sawabe⁵, Tetsuo Ushiku³

Affiliations

¹ Department of Pathology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
² Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Department of Diagnostic Pathology, NTT Medical Center Tokyo, 5-9-22 Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan. Electronic address: tmorikawa-tky@umin.ac.jp.
³ Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
⁴ Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
⁵ Department of Molecular Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

PMID: 33049447
DOI: 10.1016/j.prp.2020.153219

Abstract

B7-H3, a member of the B7 superfamily, is an immune checkpoint molecule. An association between B7-H3 expression and poor survival has been reported in many types of cancer. However, its prognostic value in patients with upper tract urothelial carcinoma (UTUC) has not yet been reported. The aim of this study was to examine the clinical significance of tumor B7-H3 expression in UTUC. B7-H3 positivity was observed in 36 of 271 cases (13 %) by immunohistochemistry and was significantly associated with several adverse clinicopathological features such as tumor grade, tumor stage, and lymph node metastasis. In addition, B7-H3 positivity was significantly associated with shorter metastasis-free survival and cancer-specific survival. We also found that B7-H3/programmed cell death ligand-1 (PD-L1) co-positivity was significantly associated with worse prognosis. These results suggest the utility of B7-H3 positivity and B7-H3/PD-L1 co-positivity as novel prognostic biomarkers in UTUC, and the potential usefulness of B7-H3 targeted therapy for patients with UTUC, the effect of which may be enhanced by combination with programmed cell death-1 /PD-L1 blockade.

Keywords: Immune checkpoint molecule; Immunohistochemistry; Prognostic biomarker; Survival rate; Upper tract urothelial carcinoma.

MeSH terms

Aged
B7 Antigens / analysis*
B7-H1 Antigen / analysis
Biomarkers, Tumor / analysis*
Carcinoma / immunology*
Carcinoma / mortality
Carcinoma / secondary
Carcinoma / surgery
Female
Humans
Immunohistochemistry
Lymphatic Metastasis
Male
Neoplasm Grading
Neoplasm Staging
Retrospective Studies
Tissue Array Analysis
Urologic Neoplasms / immunology*
Urologic Neoplasms / mortality
Urologic Neoplasms / pathology
Urologic Neoplasms / surgery
Urothelium / immunology*
Urothelium / pathology
Urothelium / surgery

Substances

B7 Antigens
B7-H1 Antigen
Biomarkers, Tumor
CD274 protein, human
CD276 protein, human