本文選題：子宮內(nèi)膜異位癥相關(guān)卵巢癌 + 預(yù)后　； 參考：《北京協(xié)和醫(yī)學(xué)院》2016年博士論文

【摘要】：目的子宮內(nèi)膜異位癥雖為最常見婦科良性疾病之一,但其具有一定惡變能力,且與卵巢透明細(xì)胞癌和子宮內(nèi)膜樣癌的發(fā)生存在密切關(guān)系,因而學(xué)界提出了“內(nèi)異癥相關(guān)卵巢癌”的概念,并認(rèn)為這是一類具有特殊起源、發(fā)生、臨床和預(yù)后表現(xiàn)的卵巢上皮性腫瘤。本研究回顧性分析背景協(xié)和醫(yī)院卵巢透明細(xì)胞癌和子宮內(nèi)膜樣癌患者的就診資料,探討合并內(nèi)異癥的上述卵巢癌患者與未合并內(nèi)異癥患者間差異,旨在揭示內(nèi)異癥相關(guān)卵巢癌的臨床預(yù)后特點。方法收集1988年至2012年在北京協(xié)和醫(yī)院婦產(chǎn)科就診的總計309例卵巢透明細(xì)胞癌和子宮內(nèi)膜樣癌病例,回顧性分析其臨床資料,包括術(shù)前臨床信息、手術(shù)病理信息和術(shù)后化療情況,并進行隨訪調(diào)查及生存分析,應(yīng)用Kaplan-Meier單因素分析篩選與預(yù)后相關(guān)危險因素,并用Cox比例風(fēng)險模型進行多因素分析以發(fā)掘影響預(yù)后的獨立因素,總結(jié)其臨床預(yù)后特點。結(jié)果回顧性病例分析結(jié)果顯示內(nèi)異癥相關(guān)卵巢透明細(xì)胞癌和子宮內(nèi)膜樣癌較一般卵巢癌具有更早的發(fā)病年齡、更多絕經(jīng)前期狀態(tài)、更低術(shù)前CA125水平、更低腫瘤分期、更高手術(shù)切凈幾率、更低的死亡率和復(fù)發(fā)率。單因素生存分析顯示年齡、月經(jīng)狀態(tài)、腫瘤分期、手術(shù)是否切凈、組織學(xué)類型及是否合并內(nèi)異癥對卵巢透明細(xì)胞癌和子宮內(nèi)膜樣癌預(yù)后有影響。多因素分析顯示月經(jīng)狀態(tài)和腫瘤分期是影響卵巢透明細(xì)胞癌和子宮內(nèi)膜樣癌總體生存率的獨立因素,腫瘤分期和手術(shù)是否切凈是影響無病生存率的獨立因素,而是否合并內(nèi)異癥不是影響卵巢透明細(xì)胞癌和子宮內(nèi)膜樣癌預(yù)后的獨立因素。結(jié)論內(nèi)異癥相關(guān)卵巢透明細(xì)胞癌和子宮內(nèi)膜癌患者較普通透明細(xì)胞癌及卵巢癌患者具有獨特的臨床特點及更好的預(yù)后。內(nèi)異癥本身并非影響透明細(xì)胞癌和子宮內(nèi)膜樣癌預(yù)后的獨立因素。目的子宮內(nèi)膜異位癥相關(guān)卵巢癌與一般卵巢癌相比具有不同的臨床和預(yù)后特點,提示它們之間可能有兩種截然不同的組織來源和發(fā)生方式。一系列針對內(nèi)異癥惡變機制的多角度研究認(rèn)為這是一個由氧化應(yīng)激、炎癥因子、性激素調(diào)控等多種復(fù)雜因素共同作用,經(jīng)過漫長演變和轉(zhuǎn)化的過程,而一些重要的分子生物學(xué)改變可能在其中起關(guān)鍵驅(qū)動作用。本研究旨在通過全外顯子測序技術(shù)分析比較經(jīng)內(nèi)異癥惡變的卵巢子宮內(nèi)膜樣癌病例不同病變階段內(nèi)分子水平改變差異,尋找惡變過程中的潛在驅(qū)動基因,以期探索子宮內(nèi)膜異位癥惡變的發(fā)生機制。方法我們通過查詢內(nèi)異癥合并卵巢子宮內(nèi)膜樣癌病例,復(fù)核其手術(shù)病理,根據(jù)Sampson及Scott診斷標(biāo)準(zhǔn)篩選由內(nèi)異癥惡變的卵巢子宮內(nèi)膜樣癌患者,經(jīng)激光捕獲顯微切割精確獲取其卵巢良性異位內(nèi)膜、卵巢不典型異位內(nèi)膜和卵巢子宮內(nèi)膜樣癌的石蠟病理標(biāo)本,提取基因組DNA并進行全外顯子組測序。通過比對不同病變階段組織內(nèi)外顯子突變差異,尋找其中潛在的關(guān)鍵突變基因。結(jié)果全外顯子組測序在卵巢良性異位內(nèi)膜、不典型異位內(nèi)膜和子宮內(nèi)膜樣癌DNA樣本中分別檢測到57911、18768和69001個單核苷酸突變(SNV)或段片段插入缺失(InDel),通過無功能突變和數(shù)據(jù)庫信息比對高頻突變過濾,在卵巢不典型內(nèi)異癥組織和內(nèi)膜樣癌組織中共發(fā)現(xiàn)21個相同外顯子突變,其中CDKN2AIP、UIMC1和TPBG基因分別參與調(diào)控細(xì)胞增殖凋亡抉擇、DNA損傷修復(fù)和Wnt信號通路。結(jié)論全外顯子組測序證實卵巢不典型內(nèi)異癥和卵巢子宮內(nèi)膜樣癌間存在相同突變基因,其中CDKN2AIP、UIMC1和TPBG等基因中某個或多個可能是內(nèi)異癥惡變至子宮內(nèi)膜樣癌過程的潛在驅(qū)動基因。
[Abstract]:Objective endometriosis is one of the most common benign gynecologic diseases, but it has a certain malignant ability, and is closely related to the occurrence of ovarian clear cell carcinoma and endometrioid carcinoma. Therefore, the concept of "endometriosis related ovarian cancer" is proposed by the academic community, and it is considered as a class of special origin, occurrence, clinical and prognosis. The present study reviewed the clinical data of patients with ovarian clear cell carcinoma and endometrioid carcinoma in the background Concorde and hospital, explored the differences between the ovarian cancer patients with endometriosis and the patients with unincorporated endometriosis, and aimed at revealing the clinical prognostic characteristics of nests associated with endometriosis. Methods collected from 1988 to 1988. A total of 309 cases of ovarian clear cell carcinoma and endometrioid carcinoma in the Department of Obstetrics and gynecology in Peking Union Medical College Hospital in 2012 were reviewed. The clinical data were analyzed retrospectively, including preoperative clinical information, surgical pathology information and postoperative chemotherapy, follow-up investigation and survival analysis. Kaplan-Meier single factor analysis should be used to screen the risk of prognosis. Risk factors, and multifactor analysis using the Cox proportional hazard model to explore independent factors that affect prognosis and summarize their clinical prognostic characteristics. Results retrospective case analysis showed that endometriosis related ovarian clear cell carcinoma and endometrioid carcinoma have earlier age of onset, more premenopausal status, lower operation than general ovarian cancer. Anterior CA125 level, lower tumor staging, higher surgical removal rate, lower mortality and recurrence rate. Univariate survival analysis showed that age, menstrual state, tumor staging, surgical removal, histologic type, and combination of endometriosis have an impact on the prognosis of ovarian clear cell carcinoma and endometrioid carcinoma. State and tumor staging are independent factors affecting the overall survival rate of ovarian clear cell carcinoma and endometrioid carcinoma. Tumor staging and surgical removal are independent factors affecting the disease free survival, and whether or not endometriosis is not an independent factor affecting the prognosis of ovarian clear cell carcinoma and endometrioid carcinoma. Nests of clear cell carcinoma and endometrial cancer have unique clinical characteristics and better prognosis than those of common clear cell and ovarian cancer. The characteristics of bed and prognosis suggest that there may be two distinct sources and ways of formation between them. A series of studies on the mechanism of malignancy of endometriosis are considered to be a complex factor, such as oxidative stress, inflammatory factors, sex hormone regulation and other complex factors, through a long process of evolution and transformation, and some important factors. Molecular biological changes may play a key driving role in this study. The aim of this study is to compare the difference in molecular level changes during different pathological stages of ovarian endometrioid carcinoma cases with malignant changes of endometriosis by exon sequencing and search for potential driving genes in the process of malignancy in order to explore the malignancy of endometriosis. Methods we reviewed the cases of endometrioid endometrioid carcinoma with endometriosis and reviewed its operation and pathology. According to the Sampson and Scott diagnostic criteria, we screened the ovarian endometrioid carcinoma patients with endometriosis and malignancy. The benign ectopic endometrium, the atypical ectopic endometrium and the ovaries of the ovaries were obtained by laser microdissection. The paraffin pathological specimens of endometrioid carcinoma of the nested endometrium were extracted from the genomic DNA and sequenced the exon group. The potential key mutations were found by comparing the differences of the intron and inside intron mutations at different pathological stages. Results the exon group was sequenced in the ovarian benign ectopic endometrium, atypical ectopic endometrium and endometrioid carcinoma DNA samples. 5791118768 and 69001 single nucleotide mutations (SNV) or segment insertion deletion (InDel) were detected, and 21 identical exons were found in the atypical endometrium and endometrioid carcinoma tissues by non functional mutation and database information, and 21 of the same exons were found in the atypical endometrium and endometrioid carcinoma tissues, including CDKN2AIP, UIMC1 and TPBG genes, respectively. The choice of cell proliferation and apoptosis, DNA damage repair and Wnt signaling pathway. Conclusion all exon sequencing confirms that the same mutations exist between ovarian atypical endometrioid and ovarian endometrioid carcinomas, and one or more of CDKN2AIP, UIMC1 and TPBG may be the potential driving force for endometrioid carcinoma. Genes.
【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】：2016
【分類號】：R711.71;R737.31

【相似文獻】

相關(guān)期刊論文 前10條

1 金曉琴;形態(tài)罕見的卵巢腫瘤1例[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2000年07期

2 覃英姿;卵巢腫瘤并發(fā)闌尾炎1例報告[J];中國校醫(yī);2000年02期

3 韓衛(wèi)紅,李青,李霞;經(jīng)陰道超聲在卵巢腫瘤診斷中的應(yīng)用[J];青島醫(yī)藥衛(wèi)生;2000年03期

4 ;卵巢腫瘤[J];國外科技資料目錄.醫(yī)藥衛(wèi)生;2000年10期

5 秦平,陳焰;二維超聲及彩色多普勒聯(lián)合應(yīng)用對卵巢腫瘤的診斷[J];中國超聲醫(yī)學(xué)雜志;2001年07期

6 王月香;超聲多普勒技術(shù)在卵巢腫瘤診斷上的新進展[J];河北醫(yī)科大學(xué)學(xué)報;2001年06期

7 崔淑莉,徐愛哲,趙世強;經(jīng)陰式彩色多普勒對卵巢腫瘤性質(zhì)判定的臨床意義[J];哈爾濱醫(yī)藥;2001年01期

8 史海英,姜勝健;卵巢腫瘤誤診13例分析[J];腫瘤防治雜志;2001年03期

9 趙信喜;微波快速石蠟切片診斷卵巢腫瘤206例分析[J];中國誤診學(xué)雜志;2001年05期

10 ;卵巢腫瘤[J];國外科技資料目錄.醫(yī)藥衛(wèi)生;2001年03期

相關(guān)會議論文 前10條

1 李利;王超英;林忠乙;;老年卵巢腫瘤82例分析[A];中國抗癌協(xié)會婦科腫瘤專業(yè)委員會第六次全國學(xué)術(shù)會議論文匯編[C];2001年

2 楊幼易;;老年婦女卵巢腫瘤手術(shù)治療140例臨床分析[A];中國抗癌協(xié)會婦科腫瘤專業(yè)委員會第六次全國學(xué)術(shù)會議論文匯編[C];2001年

3 楊帆;楊太珠;羅紅;朱琦;郭文琪;田雨;陳嬌;;生育前期女性卵巢腫瘤39例超聲診斷[A];2005年全國醫(yī)學(xué)影像技術(shù)學(xué)術(shù)會議西部論壇論文匯編[C];2005年

4 張海;李光展;吳瑛;盧俊;王慧芳;鄧偉蓮;;經(jīng)陰道彩色多普勒血流圖檢測卵巢腫瘤血管的臨床價值[A];中華醫(yī)學(xué)會第六次全國超聲醫(yī)學(xué)學(xué)術(shù)年會論文匯編[C];2001年

5 洪樹勛;許紅;曹良杰;;801例卵巢腫瘤臨床分析[A];紀(jì)念卓越的人民醫(yī)學(xué)家林巧稚大夫誕辰100周年——全國婦產(chǎn)科高級學(xué)術(shù)論壇論文集[C];2001年

6 梁元姣;葉小勤;;老年婦女雙側(cè)卵巢巨大腫瘤1例報告[A];中國抗癌協(xié)會婦科腫瘤專業(yè)委員會第六次全國學(xué)術(shù)會議論文匯編[C];2001年

7 劉力;李冰琳;張啟培;;836例卵巢腫瘤臨床病理分析[A];第八次全國婦產(chǎn)科學(xué)學(xué)術(shù)會議論文匯編[C];2004年

8 陳曉玲;紀(jì)莉;吳曉燕;魚紅菊;王琳;;彩色多普勒超聲在卵巢腫瘤診斷中的應(yīng)用[A];第一屆全國婦產(chǎn)科超聲學(xué)術(shù)會議論文匯編[C];2006年

9 許幼峰;郭e，

本文編號：1996465