1National Hospital Organization Kyoto Medical Center, Kyoto city, Kyoto, Japan.
1National Hospital Organization Kyoto Medical Center, Kyoto city, Kyoto; 2Seeds Development and Research Platform Project, Japan Agency for Medical Research and Development (AMED), Chiyoda-ku, Tokyo, Japan.
Georgian Med News. 2024 May(350):42-48.
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)/β1i develop uterine leiomyosarcoma spontaneously.
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.
In human uterine leiomyosarcoma, there was a loss of LMP2/β1i expression and enhanced cyclin E1 and Ki-67/MIB1 expression. In human uterine leiomyomas and normal uterine smooth muscle layers, enhanced LMP2/β1i expression and the disappearance of the expression of E1 and Ki-67/MIB1 were noted. The pattern of expression of each factor in other uterine mesenchymal tumors was different from that of uterine leiomyosarcoma.
LMP2/β1i, cyclin E1, and Ki-67/MIB1 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.
大多数在子宫体中发现的间叶肿瘤是良性肿瘤;然而,子宫平滑肌肉瘤是一种恶性肿瘤,其危险因素不明,且会反复复发和转移。在某些情况下,子宫平滑肌瘤和子宫平滑肌肉瘤的组织病理学表现相似,使用切除组织样本的外科病理学诊断较为困难。有必要分析人子宫平滑肌肉瘤的危险因素,并建立诊断生物标志物和治疗方法。缺乏蛋白酶体亚基低分子量肽 2(LMP2)/β1i 的雌性小鼠会自发发展为子宫平滑肌肉瘤。
在 334 名疑似子宫间质性肿瘤的患者中,从病理档案中选择诊断为子宫平滑肌肿瘤的患者。为了研究生物标志物候选因素的表达状态,用生物标志物候选因素的抗体对人子宫平滑肌肉瘤、子宫平滑肌瘤和其他子宫间质性肿瘤的薄切片进行免疫组织化学染色。
在人子宫平滑肌肉瘤中,LMP2/β1i 的表达缺失,而 cyclin E1 和 Ki-67/MIB1 的表达增强。在人子宫平滑肌瘤和正常子宫平滑肌层中,观察到 LMP2/β1i 的表达增强和 E1 和 Ki-67/MIB1 的表达消失。其他子宫间质性肿瘤中每种因素的表达模式与子宫平滑肌肉瘤不同。
LMP2/β1i、cyclin E1 和 Ki-67/MIB1 可能是人子宫平滑肌肉瘤的生物标志物候选因素。应进行更大规模的临床试验,以建立子宫间质性肿瘤的治疗和诊断方法。