Objectives: Most mesenchymal tumors found in the uterine corpus are benign tumors; however, uterine leiomyosarcoma is a malignant tumor with unknown risk factors that repeatedly recurs and metastasizes. In some cases, the histopathologic findings of uterine leiomyoma and uterine leiomyosarcoma are similar and surgical pathological diagnosis using excised tissue samples is difficult. It is necessary to analyze the risk factors for human uterine leiomyosarcoma and establish diagnostic biomarkers and treatments. Female mice deficient in the proteasome subunit low molecular mass peptide 2 (LMP2)/b1i develop uterine leiomyosarcoma spontaneously. Methodology: Out of 334 patients with suspected uterine mesenchymal tumors, patients diagnosed with smooth muscle tumors of the uterus were selected from the pathological file. To investigate the expression status of biomarker candidate factors, immunohistochemical staining was performed with antibodies of biomarker candidate factors on thin-cut slides of human uterine leiomyosarcoma, uterine leiomyoma, and other uterine mesenchymal tumors. Results: In human uterine leiomyosarcoma, there was a loss of LMP2/b1i expression and enhanced cyclin E1 and Ki-67 expression. In human uterine leiomyomas and normal uterine smooth muscle layers, enhanced LMP2/b1i expression and the disappearance of the expression of E1 and Ki-67 were noted. The pattern of expression of each factor in other uterine mesenchymal tumors was different from that of uterine leiomyosarcoma. Conclusions: LMP2/b1i, cyclin E1, and Ki-67 may be candidate factors for biomarkers of human uterine leiomyosarcoma. Further large-cohort clinical trials should be conducted to establish treatments and diagnostics for uterine mesenchymal tumors.

The authors have declared no competing interest.

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000044182

This clinical research was performed with research funding from the following: Japan Society for Promoting Science for TH (Grant No. 19K09840, 23K08881), Tokyo, Japan, and START-program Japan Science and Technology Agency for TH (Grant No. STSC20001), Tokyo, Japan and the National Hospital Organization Multicenter clinical study for TH (Grant No. 2019-Cancer in general-02), Tokyo, Japan, and The Japan Agency for Medical Research and Development (AMED) (Grant No. 22ym0126802j0001), Tokyo, Japan.

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Ethics approval and consent to participate: This study was reviewed and approved by the Central Ethics Review Board of the National Hospital Organization Headquarters in Japan (Tokyo, Japan) on November 08, 2019, and Kyoto University School of Medicine (Kyoto, Japan) on August 25, 2023, with approval codes NHO H31-02 and M192. The completion numbers for the authors are AP0000151756, AP0000151757, AP0000151769, and AP000351128. As this research was considered clinical research, consent to participate was required. After briefing regarding the clinical study and approval of the research contents, the participants signed an informed consent form. Clinical Research: A multi-center retrospective observational clinical study of subjects who underwent cancer genomic medicine at a cancer medical facility in Kyoto, Japan. This study was reviewed and approved by the Central Ethics Review Board of the National Hospital Organization Headquarters in Japan (Tokyo, Japan) on November 18, 2020, and Kyoto University School of Medicine (Kyoto, Japan) on August 24, 2022, with approval codes NHO R4-04 and M237. All participants agreed to take part in the present study. We have obtained Informed Consent Statements from people participating in clinical studies.

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