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Uterine leiomyosarcomas with osteoclast-like giant cells associated with high expression of RUNX2 and RANKL

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Abstract

Uterine leiomyosarcoma (ULMS) with osteoclast-like giant cells (OLGCs) has been reported as a rare phenomenon in ULMS, and its clinico-pathological features and tumorigenesis remain unclear. We recently reported high expression of receptor activator of nuclear factor κB ligand (RANKL) in ULMS with OLGCs. As osteoblasts produce RANKL, in this study, we analyzed the expression of Runt-related transcription factor 2 (RUNX2), a critical transcription factor for osteoblasts, and osteoclast-related proteins in three cases of ULMS with OLGCs as well as five conventional ULMSs and nine leiomyomas. Immunohistochemistry and real-time reverse transcription quantitative polymerase chain reaction analyses showed high expression of RUNX2 and RANKL in ULMS with OLGCs. In these cases, macrophages expressed receptor activator of nuclear factor κB (RANK), and OLGCs expressed osteoclast-related proteins (nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and cathepsin K). Accumulation sites of cathepsin K–positive OLGCs showed hemorrhagic appearance and degraded type IV collagen. We reviewed reported cases of ULMS with OLGCs, including ours, and found that they presented an aggressive course even at stage I. Furthermore, metastatic lesions showed similar histological features to those of OLGC association in ULMS. Here, we show that tumor cells in ULMS with OLGCs highly express RUNX2 and RANKL and that osteoclastic differentiation of macrophages occurs in the tumor tissue.

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Acknowledgments

The authors thank Ms. A. Ishikawa, Ms. M. Kataoka, and Mr. T. Arai for the expert technical assistance. We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (C) to Mika Terasaki (No. 17K11299).

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Author notes

  1. Koichi Yoneyama

    Present address: Minatomirai-Yume Clinic, 3-6-3, Minatomirai, Nishi-ku, Yokohama, Kanagawa, 220-0012, Japan

  2. Keisuke Kurose

    Present address: Kubonoya Women’s Hospital, 2-2-12, Chuou, Kashiwa, Chiba, 277-0023, Japan

Authors and Affiliations

  1. Department of Analytic Human Pathology, Nippon Medical School, 1-25-16, Nezu, Bunkyo-ku, Tokyo, 113-0031, Japan

    Mika Terasaki, Yasuhiro Terasaki, Kyoko Wakamatsu, Naomi Kuwahara, Etsuko Toda, Yoko Endo, Shinobu Kunugi, Yusuke Kajimoto & Akira Shimizu

  2. Division of Pathology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan

    Yasuhiro Terasaki

  3. Department of Obstetrics and Gynecology, Nippon Medical School Musashikosugi Hospital, 1-396, Kosugimachi, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan

    Koichi Yoneyama

  4. Department of Obstetrics and Gynecology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan

    Rieko Kawase & Keisuke Kurose

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  1. Mika Terasaki
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Contributions

All authors contributed to the study conception and design, material preparation, and data collection. Data analysis was performed by Mika Terasaki, Kyoko Wakamatsu, Naomi Kuwahara, Etsuko Toda, Yoko Endo, Shinobu Kunugi, Yusuke Kajimoto, Rieko Kawase, Keisuke Kurose, and Koichi Yoneyama. The first draft of the manuscript was written by Mika Terasaki, Yasuhiro Terasaki, and Akira Shimizu, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mika Terasaki.

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This study was performed according to the Declaration of Helsinki. The study protocol was reviewed and approved by the Human Ethics Review Committee of the Nippon Medical School (approval no. 30-01-1062).

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Terasaki, M., Terasaki, Y., Wakamatsu, K. et al. Uterine leiomyosarcomas with osteoclast-like giant cells associated with high expression of RUNX2 and RANKL. Virchows Arch 478, 893–904 (2021). https://doi.org/10.1007/s00428-020-02996-1

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