Laganà Antonio Simone, Vergara Daniele, Favilli Alessandro, La Rosa Valentina Lucia, Tinelli Andrea, Gerli Sandro, Noventa Marco, Vitagliano Amerigo, Triolo Onofrio, Rapisarda Agnese Maria Chiara, Vitale Salvatore Giovanni
Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy.
Arch Gynecol Obstet. 2017 Nov;296(5):855-867. doi: 10.1007/s00404-017-4515-5. Epub 2017 Sep 5.
Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas.
Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.
Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14-q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-β3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion.
The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future.
尽管对子宫平滑肌瘤发生和生长相关因素进行了大量研究，但这些肿瘤的发病机制仍不清楚。子宫肌层的内在异常、雌激素的异常子宫肌层受体、以及月经期激素变化或对缺血损伤的反应改变，可能是这些肿瘤中发现的（表观）遗传变化起始的原因。考虑到这些因素，我们旨在概述子宫平滑肌瘤的表观遗传和遗传状况。
叙述性综述，综合从计算机数据库检索的文献结果。
多项研究表明平滑肌瘤起源于单克隆。越来越多的证据集中在肿瘤发生的危险因素和机制上：在复发率最高的病例中发现了12号和14号染色体易位以及7号染色体长臂缺失；HMGA2基因的失调已定位在关键的12q14-q15位点。雌激素和孕激素被认为是肿瘤生长的促进剂，而环境雌激素的潜在作用尚未得到充分研究。具有促有丝分裂活性的生长因子，如转化生长因子-β3、成纤维细胞生长因子、表皮生长因子和胰岛素样生长因子-I在肌瘤中升高，可能作为肿瘤促进的效应因子发挥作用。
关于遗传学和表观遗传学以及控制正常和病理性子宫肌层细胞生物学的生长因子的新线索，可能在不久的将来对开发新的有效且侵入性较小的治疗策略有很大帮助。
