Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ankara Bilkent City Hospital, Ankara Yıldırım Beyazıt University, Ankara, Turkiye.
Department of Pathology, Ankara Bilkent City Hospital, Ankara, Turkiye.
Turk J Med Sci. 2024 Apr 16;54(4):804-810. doi: 10.55730/1300-0144.5852. eCollection 2024.
BACKGROUND/AIM: Uterine leiomyosarcomas (uLMS) are extremely rare high-grade tumors with a poor prognosis. Their etiopathogenesis remains largely unknown. The uterus is the most frequent site for LMS. uLMS and uterine leiomyoma (uLM) must frequently be differentiated in patients with a uterine mass. Nicotinamide N-methyltransferase (NNMT), a cytoplasmic protein, is involved in the progression and spread of a variety of cancer types. The expression of NNMT in a mesenchymal malignancy was not examined previously. This study represents the first investigation into NNMT expression in uLMS, uLM and benign uterine myometrium and correlates NNMT overexpression with worse prognosis in uLMS.
The expression of NNMT was investigated by immunohistochemistry on formalin-fixed paraffin-embedded tissue of uLMS in 31 patients, uLM in seven patients and benign myometrial in 31 patients.
The expression of NNMT in uLMS was markedly higher than in uLM and normal myometrial tissue (p < 0.001). The expression of NNMT in early stage uLMS was lower than in advanced stage disease (p = 0.034). NNMT expression was an independent prognostic factor in predicting recurrence-free survival in uLMS (p = 0.037).
NNMT can aid in the preoperative differentiation of uLMS and uLM. The consequences of NNMT overexpression, such as the activation and inactivation of oncoproteins and tumor suppressor proteins, respectively, as well as the enrichment of the cancer stem cell population, overlap with the major mechanisms responsible for poor prognosis in mesenchymal tumors. NNMT may be investigated further in the context of antitumor treatment in patients with mesenchymal malignancies.
背景/目的：子宫平滑肌肉瘤（uLMS）是一种罕见的高级别肿瘤，预后不良。其发病机制仍知之甚少。子宫是 LMS 最常见的部位。在患有子宫肿块的患者中，必须经常将 uLMS 和子宫平滑肌瘤（uLM）区分开来。烟酰胺 N-甲基转移酶（NNMT）是一种细胞质蛋白，参与多种癌症类型的进展和扩散。先前未检查过 NNMT 在间充质恶性肿瘤中的表达。本研究首次调查了 NNMT 在 uLMS、uLM 和良性子宫平滑肌中的表达，并将 NNMT 过表达与 uLMS 的预后不良相关联。
对 31 例 uLMS、7 例 uLM 和 31 例良性子宫平滑肌组织的福尔马林固定石蜡包埋组织进行 NNMT 的免疫组织化学检测。
uLMS 中 NNMT 的表达明显高于 uLM 和正常子宫平滑肌组织（p < 0.001）。早期 uLMS 中 NNMT 的表达低于晚期疾病（p = 0.034）。NNMT 表达是预测 uLMS 无复发生存的独立预后因素（p = 0.037）。
NNMT 可有助于术前区分 uLMS 和 uLM。NNMT 过表达的后果，例如癌蛋白和肿瘤抑制蛋白的分别激活和失活，以及癌症干细胞群体的富集，与间充质肿瘤预后不良的主要机制重叠。NNMT 可能会在间充质恶性肿瘤患者的抗肿瘤治疗中进一步研究。
