本文選題：乳腺葉狀腫瘤　切入點：良性　出處：《北京協(xié)和醫(yī)學(xué)院》2015年博士論文　論文類型：學(xué)位論文

【摘要】：目的：初步探討乳腺葉狀腫瘤三種組織學(xué)類型間臨床特征方面的差異及影響葉狀腫瘤無病生存情況的因素。研究方法：回顧性分析我院2002年1月至2012年12月間收治的共246例女性乳腺葉狀腫瘤患者的相關(guān)臨床資料,包括患者發(fā)病年齡、就診年齡、病程、初治腫瘤大小、腫瘤部位、病理類型、有無潰瘍、初治手術(shù)時間及方式、有無局部復(fù)發(fā)或遠處轉(zhuǎn)移、有無纖維腺瘤病史、復(fù)發(fā)期間有無病理改變、局部復(fù)發(fā)次數(shù)及術(shù)后治療。并進行隨訪至2014-5-20日。中位隨訪時間為48個月,56例出現(xiàn)局部復(fù)發(fā),5例出現(xiàn)遠處轉(zhuǎn)移,1例局部復(fù)發(fā)伴遠處轉(zhuǎn)移。65人失訪,失訪率為26%。結(jié)果：乳腺葉狀腫瘤三種組織學(xué)類型間單因素分析,發(fā)現(xiàn)發(fā)病年齡,就診年齡,初治腫瘤大小,有無潰瘍,初治手術(shù)方式及有無遠處轉(zhuǎn)移P值均0.05(P=0.014,P=0.018,P0.000, P=0.003, P0.000, P=0.001),即三種組織學(xué)類型的葉狀腫瘤在上述方面存在差異,且差異有統(tǒng)計學(xué)意義。而無病生存時間及有無復(fù)發(fā)P值分別為0.055及0.060,接近0.05,趨向于有統(tǒng)計學(xué)差異。多因素分析采用有序多分類Logistic回歸,模型中有無遠處轉(zhuǎn)移及局部腫物切除P值分別為0.041及0.018,均0.05,表現(xiàn)為有統(tǒng)計學(xué)差異。而初治腫瘤大小P值為0.052,趨向于有統(tǒng)計學(xué)差異。在研究乳腺葉狀腫瘤無病生存的預(yù)測因素時,Kaplan-Meier單因素分析發(fā)現(xiàn),有無纖維腺瘤病史為預(yù)測葉狀腫瘤復(fù)發(fā)的危險因素,P值0.000.而局部腫物切除術(shù)比乳腺單純切除及改良根治術(shù)有著更高的局部復(fù)發(fā)率,P值為0.043。且三種病理類型葉狀腫瘤的復(fù)發(fā)風(fēng)險,惡性交界性良性,且P值為0.083,趨向于有統(tǒng)計學(xué)意義。Cox多因素模型中,手術(shù)方式、有無纖維腺瘤病史及病理類型均有統(tǒng)計學(xué)意義,P值分別為0.009、0.001及0.000。結(jié)論：良性、交界性及惡性乳腺葉狀腫瘤間在有無遠處轉(zhuǎn)移、初治手術(shù)方式及初治腫瘤大小方面存在差異,即腫瘤惡性程度越高,腫瘤越大,越容易出現(xiàn)遠處轉(zhuǎn)移。手術(shù)方式、有無纖維腺瘤病史及病理類型是影響乳腺葉狀腫瘤無病生存的獨立預(yù)后因素。目的：本研究的目的是分析miR-498、miR-let-7d5p、miR-let-7d3p、miR-let-7e5p及miR-let-7e3p在乳腺浸潤性導(dǎo)管癌中的表達及其與臨床病理特征的關(guān)系。方法：前期研究中,我們利用Snail誘導(dǎo)永生化的乳腺癌細胞系MCF-10A發(fā)生EMT,然后利用miRNA芯片分析發(fā)生EMT前后MCF-10A中miRNA的表達情況,發(fā)現(xiàn)miR-498在EMT后表達量明顯升高,說明這個miRNA可能對EMT有促進作用。另外,我們構(gòu)建了一個含有1000多種microRNAs前體的病毒庫,然后用該病毒庫去感染非轉(zhuǎn)移性乳腺癌細胞系MCF-7,通過Transwell侵襲實驗去選擇并富集這些透膜細胞,并形成單克隆。最后,對這些單克隆進行microRNAs測序,發(fā)現(xiàn)了一些對細胞侵襲轉(zhuǎn)移可能具有促進作用的microRNAs,其中包括miR-let-7d及miR-let-7e。然后,利用RT-PCR技術(shù),檢測miR-49、 miR-let-7d5p、 miR-let-7d3p、 miR-let-7e5p及miR-let-7e3p在正常乳腺組織及乳腺癌組織中的表達,并同時收集這些乳腺癌患者的臨床病理資料。結(jié)果：相比乳腺正常組織,miR-498、miR-let-7d3p及miR-let-7e3p在乳腺癌中的表達下調(diào),且差異有統(tǒng)計學(xué)意義(P=0.0004,0.0012及0.0453)。miR-let-7d3p在乳腺癌組織中的表達與患者月經(jīng)初潮年齡、P53及脈管瘤栓呈相關(guān)性(P=0.0177,0.0044及0.0166)。miR-let-7e5p在乳腺癌組織中的表達與ER、PR、EGFR及分子分型有相關(guān)性(P=0.0091,0.0096,0.0166及0.0287),但與Her-2表達及Ki-67指數(shù)無關(guān)(P=0.6733,P=0.8121),與CK56有相關(guān)趨勢(P=0.0550)。miR-let-7e3p在乳腺癌組織中的表達與脈管瘤栓呈相關(guān)性(P=0.0398)。結(jié)論：miR-498、miR-let-7d3p及miR-let-7e3p在乳腺浸潤性導(dǎo)管癌中可能具有抑癌作用。miR-let-7d3p在月經(jīng)初潮晚、無脈管瘤栓及P53陽性的乳腺癌患者中表達量高,其與P53的具體相互作用機制不詳,但前者提示,miR-let-7d3p在乳腺癌中是一種保護性因素。miR-let-7e5p在ER(+)、PR (+)、CK56 (-)、EGFR (-)及Luminal型乳腺癌中高表達,提示miR-let-7e5p在乳腺癌中是一種保護性因素,且miR-let-7e5p與ER、PR、CK56及EGFR間的相互聯(lián)系及作用機制,有待于進一步研究。miR-let-7e3p與脈管瘤栓成負相關(guān),提示miR-let-7e3p在乳腺癌中可能具有抑制轉(zhuǎn)移的作用。
[Abstract]:Objective: To investigate the difference factors of phyllodes tumor of the breast three histological types between the clinical characteristics and influence of phyllodes tumor disease free survival. Methods: retrospective analysis of our hospital from January 2002 to December 2012 were a total of 246 cases of female patients with breast phyllodes tumor related clinical data, including age, age of patients. The course of treatment, tumor size, tumor location, pathological type, ulceration, initial treatment and operation time, there is no local recurrence or distant metastasis, there is no recurrence during the history of fibroadenoma, without pathological changes, the number of local recurrence and postoperative treatment. And follow-up to 2014-5-20 days. The median follow-up time 48 months, 56 cases had local recurrence and metastasis occurred in 5 cases, 1 cases of local recurrence and distant metastasis.65 people lost, the lost rate was 26%. results: three breast phyllodes tumor histological types The single factor analysis found that the age of onset, age, initial treatment of ulceration, tumor size, initial treatment of surgery and metastasis P values were 0.05 (P=0.014, P=0.018, P0.000, P=0.003, P0.000, P=0.001), namely the three histological types of phyllodes tumor differences in the above aspects, there were and the difference of disease-free survival and recurrence P values were 0.055 and 0.060, close to 0.05, tend to have significant differences. Multivariate analysis using Logistic regression model, there is no distant metastasis and local tumor resection P values were 0.041 and 0.018, 0.05, performance there were significant differences in tumor size and initial treatment. The P value is 0.052, tend to have significant differences. No predictors of survival in the study of breast phyllodes tumors, Kaplan-Meier single factor analysis found that there is no history for the prediction of fibroadenoma of phyllodes tumor recurrence The risk factors of P value, 0.000. and local tumor resection than mastectomy and modified radical mastectomy with higher rates of local recurrence, P value of the risk of recurrence of 0.043. and three kinds of pathological types of malignant phyllodes tumor, borderline and benign, P value is 0.083, tend to have statistical significance in multivariate.Cox model there is no way, surgery, history of fibroadenoma and pathological types were statistically significant, P = 0.009,0.001 and 0.000. conclusion: benign, borderline and malignant phyllodes tumors of the breast in metastasis, initial treatment of surgery and early treatment of tumor size differences, namely the higher degree of malignancy, tumor size and more prone to distant metastasis. There is no history of surgery, fibroadenoma and pathological types were independent prognostic factors of breast phyllodes tumor free survival. Objective: the purpose of this study is to analyze miR-498, miR-let-7d5p, M IR-let-7d3p, miR-let-7e5p and miR-let-7e3p in breast invasive ductal carcinoma and its relationship with clinical pathological features. Methods: Based on the previous research, we use Snail induced breast cancer cell lines immortalized MCF-10A EMT, and then use the miRNA chip analysis of expression of MCF-10A in miRNA before and after EMT, miR-498 expression in EMT the amount was increased, the miRNA may contribute to EMT. In addition, we constructed a microRNAs precursor containing more than 1000 kinds of virus database, and then use the virus to infect non metastatic breast cancer cell line MCF-7 by Transwell invasion assay to select and enrichment of these cell membrane permeability, and the formation of monoclonal. Finally, microRNAs sequencing was performed on these monoclonal, discovered may promote the invasion and metastasis of microRNAs cells, including miR-let-7d and miR-let-7 E. then, using the technology of RT-PCR, miR-let-7d5p, miR-let-7d3p, miR-49 detection, the expression of miR-let-7e5p and miR-let-7e3p in normal breast tissue and breast cancer tissues, and also collected clinical data of these patients with breast cancer. Results: compared with normal breast tissue, miR-498, expression of miR-let-7d3p and miR-let-7e3p in breast cancer, was statistically significant and the difference (P=0.0004,0.0012 and 0.0453).MiR-let-7d3p expression in breast carcinoma patients with age at menarche and menstruation, P53 and vascular tumor thrombus (P=0.0177,0.0044 and 0.0166) were correlated with the expression of ER,.MiR-let-7e5p in breast cancer PR, EGFR and molecular typing correlation (P=0.0091,0.0096,0.0166 and 0.0287), but not with the expression of Her-2 and the Ki-67 index (P=0.6733, P=0.8121), a trend with CK56 (P=0.0550).MiR-let-7e3p expression in breast cancer tissue and vascular tumor Bolt is correlation (P=0.0398). Conclusion: miR-498, miR-let-7d3p and miR-let-7e3p in invasive breast may have a tumor suppressor role of.MiR-let-7d3p in the late menarche ductal carcinoma, no expression of tumor thrombus and P53 positive breast cancer patients was high, and P53 specific interaction mechanism is unknown, but the former suggested that miR-let-7d3p is a protective factor of.MiR-let-7e5p in ER in breast cancer (+), PR (+), CK56 (-), EGFR (-) high expression and Luminal type of breast cancer, suggesting that miR-let-7e5p is a protective factor in breast cancer, and miR-let-7e5p and ER, PR, mutual relation and effect the mechanism of CK56 and EGFR, need to be further studied.MiR-let-7e3p negatively correlated with vascular invasion, suggesting miR-let-7e3p could inhibit metastasis in breast cancer.

【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】：R737.9

【參考文獻】

相關(guān)期刊論文 前7條

1 Binhua P.Zhou;;Epithelial-mesenchymal transition in breast cancer progression and metastasis[J];癌癥;2011年09期

2 Jing Wei;Yu-Ting Tan;Yu-Cen Cai;Zhong-Yu Yuan;Dong Yang;Shu-Sen Wang;Rou-Jun Peng;Xiao-Yu Teng;Dong-Geng Liu;Yan-Xia Shi;;Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center[J];Chinese Journal of Cancer;2014年10期

3 吳暉;歐陽取長;曾亮;;年輕女性乳腺癌臨床特點及其預(yù)后分析[J];中華腫瘤防治雜志;2010年14期

4 范磊;邵增務(wù);吳強;魏玉龍;于曉巍;;MicroRNA-145對骨肉瘤細胞增殖及凋亡的影響[J];中國癌癥雜志;2012年04期

5 呂淑華;牛昀;;乳腺葉狀腫瘤[J];中國腫瘤臨床;2006年03期

6 陳萬青;張思維;鄭榮壽;曾紅梅;鄒小農(nóng);趙平;吳良有;李光琳;赫捷;;中國2009年惡性腫瘤發(fā)病和死亡分析[J];中國腫瘤;2013年01期

7 霍蘭茹;劉佩芳;徐熠琳;李小康;邵真真;朱鷹;;乳腺葉狀腫瘤超聲表現(xiàn)與病理相關(guān)性研究[J];中國腫瘤臨床;2014年09期

，

本文編號：1615619