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

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 O...

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Bibliographic Details
Published in:Virchows Archiv : an international journal of pathology 2021-05, Vol.478 (5), p.893-904
Main Authors: Terasaki, Mika, Terasaki, Yasuhiro, Wakamatsu, Kyoko, Kuwahara, Naomi, Yoneyama, Koichi, Kawase, Rieko, Kurose, Keisuke, Toda, Etsuko, Endo, Yoko, Kunugi, Shinobu, Kajimoto, Yusuke, Shimizu, Akira
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Biomedical materials
Cathepsin K
Cathepsin K - analysis
Cbfa-1 protein
Cell Differentiation
Collagen (type IV)
Core Binding Factor Alpha 1 Subunit - analysis
Core Binding Factor Alpha 1 Subunit - genetics
Female
Fibroids
Giant cells
Giant Cells - chemistry
Giant Cells - pathology
Hemorrhage
Humans
Immunohistochemistry
Leiomyosarcoma - chemistry
Leiomyosarcoma - genetics
Leiomyosarcoma - secondary
Lymphocytes
Macrophages
Medicine
Medicine & Public Health
Metastases
Middle Aged
NF-AT protein
NFATC Transcription Factors - analysis
Original Article
Osteoblasts
Osteoclastogenesis
Osteoclasts
Osteoclasts - chemistry
Osteoclasts - pathology
Pathology
Phenotype
Polymerase chain reaction
Proteins
RANK Ligand - analysis
RANK Ligand - genetics
Receptors
Reverse transcription
TRANCE protein
Transcription factors
Tumor cells
Tumorigenesis
Tumors
Up-Regulation
Uterine Neoplasms - chemistry
Uterine Neoplasms - genetics
Uterine Neoplasms - pathology
Uterus
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Summary: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.
ISSN:0945-6317
1432-2307
DOI:10.1007/s00428-020-02996-1