静脉内平滑肌瘤病临床特点及发病机制探索

发布时间：2018-09-09 16:09

【摘要】：静脉内平滑肌瘤病(intravenous leiomyomatosis, IVL)是一种特殊的子宫平滑肌细胞肿瘤,甚至可以延伸至下腔静脉、右心,严重者可引起猝死。IVL临床表现缺乏特异性,早期诊断困难,往往造成漏诊、误诊。因此探索其发病特点,寻找特异的分子标记物以帮助早期诊断IVL,成为亟需解决的问题。本研究首先收集了我院2002年至2014年就诊的46例IVL患者病例资料,建立IVL病例资料数据库,总结分析了其临床发病特点及预后相关因素。然后采用先进的基因芯片技术及免疫组织化学染色方法,获取IVL基因组拷贝数变异(copy number variation, CNV),并筛选与IVL发病相关的分子标记物。结果：(1)侵犯盆腔外大血管的IVL病例占56.5%。未侵犯盆腔外大血管的IVL患者中术前误诊为子宫肌瘤的占85%。是否切除双卵巢对IVL预后有显著影响(P=0.01)。是否侵犯大血管(P=0.525),年龄(P=0.579),盆腔肿物大小(P=0.352),术前CA125水平(P=0.435),初次手术是否将瘤灶切净(P=0.130),初次术后是否应用激素治疗(P=0.083)对生存曲线的影响无统计学差异。(2)IVL及子宫肌瘤肿瘤组织中均存在大量CNV。在3例IVL肿瘤组织中100%存在,在2例普通子宫肌瘤组织中均不存在的CNV如下：1p36.11:MDS2,2q34:ERBB4,5q31.1:KIF3a, 1p36.13:PAX7。(3)16例IVL及子宫肌瘤肿瘤组织ER、PR表达均为阳性,强度无统计学差异(P=0.326 P=0.109)。Ki-67阳性指数均小于3%,表达无统计学差异(P=0.174)。ERBB4阳性率：IVL7.7%,子宫肌瘤0,无统计学差异(P=0.109)。VEGF在IVL表达阳性强度显著高于子宫肌瘤(P=0.005)。上述结果表明：(1)IVL临床表现不特异,容易造成漏诊、误诊。手术是IVL治疗最重要的手段,切除双卵巢可以显著降低复发率,延长复发间隔。(2)IVL肿瘤组织中存在大量CNV,可能在IVL发病中起到重要作用。(3)目前常用分子标记物ER、PR、Ki-67均不能特异提示IVL,IVL肿瘤组织中大量的微血管使得其VEGF表达增高,但对其诊断作用有限。目前尚缺乏IVL诊断的特异性分子标记物。
[Abstract]:Intravenously leiomyomatosis (intravenous leiomyomatosis, IVL) is a special type of uterine smooth muscle cell tumor, which can even extend to the inferior vena cava, right heart. In severe cases, sudden death can be caused by lack of specificity, early diagnosis is difficult, and missed diagnosis is often caused. Misdiagnosis Therefore, it is urgent to explore the characteristics of the disease and to find specific molecular markers to help the early diagnosis of IVL,. The data of 46 cases of IVL from 2002 to 2014 in our hospital were collected and the data base of IVL cases was established. The clinical characteristics and prognostic factors were summarized and analyzed. Then the IVL genomic copy number variant (copy number variation, CNV), was obtained by using advanced gene chip technique and immunohistochemical staining method and the molecular markers related to the pathogenesis of IVL were screened. Results: (1) 56.5 cases of IVL were involved in extrapelvic vessels. 85 cases of IVL were misdiagnosed as hysteromyoma before operation. The prognosis of IVL was significantly affected by the removal of both ovaries (P0. 01). (2) IVL and hysteromyoma had no effect on survival curve after primary operation (P0. 025), age (P0. 579), pelvic tumor size (P0. 352), preoperative CA125 level (P0. 435), primary resection of tumor focus (P0. 130) and primary postoperative hormone therapy (P0. 083). There is a large amount of CNV. in tumor tissue. In 3 cases of IVL tumors, 100% of them were present, and 2 cases of normal uterine leiomyoma tissues did not exist, as follows: 1: 1p36.11: MDS2: 2q34: ERBB4: 5q31.1KIF3a. 1p36.13: PAX7. (3) 16 cases of IVL and uterine leiomyoma tissues were positive for ER,PR expression. There was no significant difference in intensity (P0. 326, P0. 109). Ki-67 positive index was lower than 3. There was no significant difference in the expression of Ki 67. There was no significant difference in the positive rate of IVL expression in uterine leiomyoma (P0. 109). The positive rate of ERBB4 was significantly higher than that in uterine leiomyoma (P0. 005), and there was no statistical difference (P0. 109) .VEGFin expression in IVL was significantly higher than that in uterine leiomyoma (P0.005). The results showed that: (1) the clinical manifestations of IVL were not specific, which easily caused misdiagnosis and missed diagnosis. Surgery is the most important treatment for IVL, and biovarectomy can significantly reduce the recurrence rate. (2) the presence of a large number of CNV, in the tumor tissues of IVL may play an important role in the pathogenesis of IVL. (3) ER,PR,Ki-67, a molecular marker commonly used at present, can not specifically suggest that a large number of microvessels in the tumor tissues of IVL,IVL can increase the expression of VEGF. However, its diagnostic value is limited. At present, there is a lack of specific molecular markers for the diagnosis of IVL.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R737.33

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