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Tumor B7-H3 expression in diagnostic biopsy specimens and survival in patients with metastatic prostate cancer

Prostate Cancer and Prostatic Diseases volume 24, pages 767–774 (2021)Cite this article

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Abstract

Background

Prostate cancer spans a broad spectrum from indolent to deadly disease. In the management of prostate cancer, diagnostic biopsy specimens are important sources of data that inform the selection of treatment. B7-H3 (CD276), an immune checkpoint molecule, has emerged as a promising immunotherapy target. B7-H3 expression is related to adverse clinical outcomes in various types of cancer; however, little is known concerning the association between tumor B7-H3 expression in diagnostic biopsy specimens and clinical outcome in patients with metastatic prostate cancer.

Methods

We evaluated tumor B7-H3 expression levels in diagnostic biopsy specimens from 135 patients with metastatic prostate cancer and 113 patients with localized prostate cancer.

Results

High B7-H3 expression was more frequently observed in patients with metastatic cancer than in those with localized cancer (31 vs. 12%; p = 0.0003). In patients with localized cancer, the B7-H3 expression status was not associated with biochemical recurrence-free survival. However, among patients with metastatic cancer, high B7-H3 expression was independently associated with high disease-specific mortality (multivariable hazard ratio [HR] = 2.72; p = 0.047) and overall mortality rates (multivariable HR = 2.04; p = 0.025).

Conclusions

Tumor B7-H3 expression in diagnostic biopsy specimens may be a useful biomarker for identifying highly aggressive metastatic prostate cancer. Given the potential utility of anti-B7-H3 immunotherapy, this information may aid in stratifying prostate cancer based on its responsiveness to B7-H3-targeted treatment.

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Fig. 1: Immunohistochemical analysis of membranous tumor B7-H3 expression in diagnostic biopsy specimens.
Fig. 2: Kaplan–Meier curves for survival in patients with metastatic prostate cancer according to tumor B7-H3 expression status (low vs. high).
Fig. 3: Kaplan–Meier curves for disease-specific survival in patients with metastatic prostate cancer according to tumor B7-H3 expression status (low vs. high) stratified by patient age (<70 years vs. ≥70 years).

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Acknowledgements

The authors thank Mr. Motoyoshi Iwakoshi, Ms. Miyuki Kogure, Ms. Tomoyo Kakita, and Mr. Shuhei Ishii for their technical assistance, and Ms. Kyoko Yamada and Ms. Yuki Takano for their secretarial expertise. The authors thank Daiichi Sankyo Co., Ltd. for providing us with anti-B7-H3 antibody (clone: BD/5A11) and B7-H3 subfamily cell array.

Funding information

This study was supported financially by JSPS KAKENHI Grant Number 19K07426 (to KI), Takeda Science Foundation (to KI), The Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care (to KI), The Mochida Memorial Foundation for Medical and Pharmaceutical Research (to KI), and Suzuki Foundation for Urological Medicine (to KI).

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Authors and Affiliations

  1. Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

    Gulanbar Amori, Emiko Sugawara, Yasuyuki Shigematsu, Masashi Akiya, Junko Kunieda, Kengo Takeuchi & Kentaro Inamura

  2. Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Gulanbar Amori, Emiko Sugawara, Yasuyuki Shigematsu, Masashi Akiya, Kengo Takeuchi & Kentaro Inamura

  3. Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Junko Kunieda

  4. Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Takeshi Yuasa, Shinya Yamamoto & Junji Yonese

  5. Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

    Kengo Takeuchi

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Contributions

KI conceived and designed the study. GA, ES, YS, MA, JK, TY, SY, JY, KT, and KI contributed to the acquisition of clinical and tumor tissue data. KI performed data analyses. GA, ES, YS, MA, JK, and KI contributed to the interpretation of the findings. GA and KI drafted the manuscript. All authors contributed to revisions of the manuscript and read and approved the final draft.

Corresponding author

Correspondence to Kentaro Inamura.

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Conflict of interest

KI received research grants from Konica Minolta, Inc. and Daiichi Sankyo Co., Ltd. TY received remuneration for a lecture from Astellas, Sanofi Japan, Pfizer Japan, Novartis Pharma Japan, Ono Pharma, Bristol-Myers Squibb Japan, and Daiichi Sankyo. All other authors declare no conflict of interest.

Ethical approval and consent to participate

This study was performed with the approval of the institutional review board of Japanese Foundation for Cancer Research (ethic code: 2018-1177). All patients included in this study provided informed consent for the research. This study was performed in accordance with the Declaration of Helsinki.

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Amori, G., Sugawara, E., Shigematsu, Y. et al. Tumor B7-H3 expression in diagnostic biopsy specimens and survival in patients with metastatic prostate cancer. Prostate Cancer Prostatic Dis 24, 767–774 (2021). https://doi.org/10.1038/s41391-021-00331-6

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