【摘要】：靜脈內(nèi)平滑肌瘤病(intravenous leiomyomatosis, IVL)是一種特殊的子宮平滑肌細(xì)胞腫瘤,甚至可以延伸至下腔靜脈、右心,嚴(yán)重者可引起猝死。IVL臨床表現(xiàn)缺乏特異性,早期診斷困難,往往造成漏診、誤診。因此探索其發(fā)病特點,尋找特異的分子標(biāo)記物以幫助早期診斷IVL,成為亟需解決的問題。本研究首先收集了我院2002年至2014年就診的46例IVL患者病例資料,建立IVL病例資料數(shù)據(jù)庫,總結(jié)分析了其臨床發(fā)病特點及預(yù)后相關(guān)因素。然后采用先進(jìn)的基因芯片技術(shù)及免疫組織化學(xué)染色方法,獲取IVL基因組拷貝數(shù)變異(copy number variation, CNV),并篩選與IVL發(fā)病相關(guān)的分子標(biāo)記物。結(jié)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患者中術(shù)前誤診為子宮肌瘤的占85%。是否切除雙卵巢對IVL預(yù)后有顯著影響(P=0.01)。是否侵犯大血管(P=0.525),年齡(P=0.579),盆腔腫物大小(P=0.352),術(shù)前CA125水平(P=0.435),初次手術(shù)是否將瘤灶切凈(P=0.130),初次術(shù)后是否應(yīng)用激素治療(P=0.083)對生存曲線的影響無統(tǒng)計學(xué)差異。(2)IVL及子宮肌瘤腫瘤組織中均存在大量CNV。在3例IVL腫瘤組織中100%存在,在2例普通子宮肌瘤組織中均不存在的CNV如下：1p36.11:MDS2,2q34:ERBB4,5q31.1:KIF3a, 1p36.13:PAX7。(3)16例IVL及子宮肌瘤腫瘤組織ER、PR表達(dá)均為陽性,強(qiáng)度無統(tǒng)計學(xué)差異(P=0.326 P=0.109)。Ki-67陽性指數(shù)均小于3%,表達(dá)無統(tǒng)計學(xué)差異(P=0.174)。ERBB4陽性率：IVL7.7%,子宮肌瘤0,無統(tǒng)計學(xué)差異(P=0.109)。VEGF在IVL表達(dá)陽性強(qiáng)度顯著高于子宮肌瘤(P=0.005)。上述結(jié)果表明：(1)IVL臨床表現(xiàn)不特異,容易造成漏診、誤診。手術(shù)是IVL治療最重要的手段,切除雙卵巢可以顯著降低復(fù)發(fā)率,延長復(fù)發(fā)間隔。(2)IVL腫瘤組織中存在大量CNV,可能在IVL發(fā)病中起到重要作用。(3)目前常用分子標(biāo)記物ER、PR、Ki-67均不能特異提示IVL,IVL腫瘤組織中大量的微血管使得其VEGF表達(dá)增高,但對其診斷作用有限。目前尚缺乏IVL診斷的特異性分子標(biāo)記物。
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R737.33

【共引文獻(xiàn)】

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