本文關(guān)鍵詞： 宮頸上皮內(nèi)瘤變 Geminin Cdt1 mRNA 宮頸上皮內(nèi)瘤變 Geminin P16 Ki67 HPV 宮頸上皮內(nèi)瘤變 宮頸錐切術(shù) 全子宮切除術(shù) 陰道殘端　出處：《南京醫(yī)科大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：第一部分細胞周期因子Geminin與Cdt1的mRNA在宮頸上皮內(nèi)瘤變組織中的表達研究目的:探討細胞周期因子Geminin與Cdt1的mRNA在宮頸癌前病變的發(fā)生、發(fā)展中的作用,為宮頸癌前病變的篩查、隨訪及預(yù)后評估提供新的生物學(xué)指標。方法:宮頸病變患者共210例為研究對象(CINⅠ、Ⅱ、Ⅲ組織各70例),陰道鏡下病變周圍區(qū)域組織病理證實為粘膜慢性炎55例作為宮頸炎癥組。因子宮肌瘤或子宮腺肌癥住院行全子宮切除術(shù)的宮頸組織30例為正常對照組,術(shù)前TCT、HPV檢查均陰性,年齡22-65歲,平均38± 12.5歲,宮頸標本均經(jīng)病理證實明確診斷,且均未接受過化療、免疫及放射等治療,取材前均征得患者知情同意,此研究獲得江蘇省人民醫(yī)院倫理委員會批準。采用RT-PCR法檢測宮頸正常組,宮頸炎癥組,CINⅠ組、CINⅡ及CINⅢ組中Geminin及Cdt1 mRNA的表達量。結(jié)果:GemininmRNA在正常宮頸組織、宮頸炎癥、CINⅠ級、CINⅡ級、CINⅢ級五組中表達量分別為 0.56±0.00、0.48±0.10、2.23±0.23、3.48±0.54、5.07±0.28。Cdt1 mRNA 表達量分別為:1.11±0.00、1.01±0.58、2.87±1.24、4.09± 1.64、5.52± 1.36。隨著CIN等級的增高,Geminin及Cdt1 mRNA的表達逐漸升高,組間比較及與正常組、宮頸炎癥組比較差異均有統(tǒng)計學(xué)意義(p0.05),正常宮頸與宮頸炎癥組比較無統(tǒng)計學(xué)意義(p0.05)。結(jié)論:細胞周期因子Geminin與Cdt1 mRNA在宮頸病變組織中表達異常,并與病變程度呈正相關(guān),說明HPV感染后通過改變細胞周期因子的表達而干擾宮頸上皮細胞增生周期,進而發(fā)生上皮內(nèi)瘤變甚至癌變,為進一步研究HPV致癌的發(fā)病機制提供幫助,為臨床盡早明確診斷、預(yù)測宮頸病變提供可能的生物學(xué)參數(shù)。第二部分Geminin與p16、Ki67在宮頸上皮內(nèi)瘤變組織的差異表達及與HPV關(guān)系的研究目的:探討細胞周期因子Geminin與p16、Ki67在宮頸病變組織的差異表達,比較Geminin與p16、Ki67在宮頸病變中的診斷及預(yù)測價值,及其與HPV感染的相關(guān)性。方法:宮頸病變患者共210例為研究對象(CINⅠ、Ⅱ、Ⅲ組織各70例),陰道鏡下病變周圍區(qū)域組織病理證實為粘膜慢性炎55例作為宮頸炎癥組。因子宮肌瘤或子宮腺肌癥住院行全子宮切除術(shù)的宮頸組織30例為正常對照組,術(shù)前TCT、HPV檢查均陰性,年齡22-65歲,平均38±12.5歲,宮頸標本均經(jīng)病理證實明確診斷,且均未接受過化療、免疫及放射等治療,取材前均征得患者知情同意,此研究獲得江蘇省人民醫(yī)院倫理委員會批準。采用免疫組化方法法檢測宮頸正常,宮頸炎癥,CINⅠ、CIN及CINⅢ組織中Geminin、p16及Ki67的差異表達、采用HC2的方法檢測HPV的載量。結(jié)果:Geminin、P16在正常宮頸及宮頸炎組織中無陽性或弱陽性表達。Geminin在 CINⅠ、CINⅡ、CINⅢ 中的陽性表達分別為 12.9%、54.3%、92.9%(p0.05);P16的陽性率為15.7%、61.4%、87.1%(p0.05)。Ki67在正常宮頸及宮頸炎組織中分別有3.3%及5.5%陽性表達,在CINⅠ、CINⅡ、CINⅢ中有35.7%、82.9%、95.7%陽性表達(p0.05)。隨著CIN等級的增高,Geminin及p16、Ki67的表達逐漸升高,組間比較及與正常組、宮頸炎癥組比較差異均有統(tǒng)計學(xué)意義(p0.05),正常宮頸與宮頸炎癥組比較無統(tǒng)計學(xué)意義(p0.05)。HPV在宮頸炎、CINⅠ、CINⅡ、CINⅢ 組織中位數(shù)分別53.2、118.2、354.6、489.7(p0.05)。Geminin 的特異度及陽性預(yù)測值最高。Geminin、Ki67的異常表達與HPV感染有相關(guān)性。結(jié)論:Geminin對宮頸上皮內(nèi)瘤變程度的靈敏度略低于P16、Ki67,但特異度、陽性預(yù)測值均高于P16、Ki67,而陰性預(yù)測值及精確度介于P16與Ki67之間,Geminin及Ki67的表達與HPV的感染呈正相關(guān),而p16的表達與HPV的感染無相關(guān)性。提示Geminin在臨床對宮頸病變診斷方面更有優(yōu)越性,在宮頸病變組織中可考慮作為新的細胞周期因子指標來協(xié)助早期、精確的診斷和預(yù)測宮頸病變。第三部分宮頸高級別瘤變行全子宮切除術(shù)相關(guān)臨床病理參數(shù)探討目的:分析宮頸高級別瘤變患者行全子宮切除術(shù),術(shù)前宮頸細胞學(xué)的分布、HPV的載量、宮頸活檢組織病理與陰道鏡、宮頸錐切的符合率,及宮頸錐切切緣陽性與病灶殘留的相關(guān)性,以及術(shù)后陰道殘端病變發(fā)生的風(fēng)險,為臨床評估CINⅡ-Ⅲ患者全子宮切除的必要性及陰道殘端隨訪提供依據(jù)。方法:收集了 368例因CINⅡ-Ⅲ行全子宮切除的患者,分別從宮頸細胞學(xué)、HPV與宮頸病變的相關(guān)性、陰道鏡判斷與宮頸活檢病理的符合率、宮頸錐切術(shù)后切緣陽性與全子宮切除術(shù)后病理結(jié)果的對比、陰道殘端日后隨訪情況等多方面回顧分析。結(jié)果:所有患者TCT檢查結(jié)果中ASCUS的比例最高(40.5%),但不同細胞學(xué)結(jié)果之間HPV的載量之間差異無統(tǒng)計學(xué)意義(p0.05)。宮頸錐切術(shù)切緣陽性的病例,與全子宮切除術(shù)后病灶殘留有直接相關(guān)性(p0.05)。陰道殘端發(fā)生VAIN的比例為11.1%符合發(fā)病率。結(jié)論:宮頸高級別瘤變患者行全子宮切除術(shù)需個體化處理,對陰道殘端的隨訪不可忽視。
[Abstract]:Objective to study expression of Geminin and Cdt1 mRNA of the first part of the cell cycle factor in cervical intraepithelial neoplasia: a study of Geminin and Cdt1 cell cycle factor mRNA in cervical precancerous lesions, the effect of the development, for the screening of cervical precancerous lesions, provide a new biological marker to evaluate prognosis. Patients with cervical lesions: a total of 210 cases as the research object (CIN I, II, III group 70 cases each), colposcopy and pathology for regional organizations around the lesion mucosa of 55 cases of chronic inflammation as the inflammation group. Because of uterine myoma or adenomyosis hospital received hysterectomy for 30 cases of normal cervical tissue the control group, preoperative TCT, HPV were negative, 22-65 years old, average 38 + 12.5 years, cervical specimens were pathologically confirmed diagnosis, and had not received chemotherapy, immune and radiation therapy, patients were drawn before the consent of the informed consent. Study on the approval of the ethics committee of Jiangsu Province People's Hospital. RT-PCR method was used to detect cervical inflammation group, normal group, CIN group, the expression of CIN II and CIN in Geminin and Cdt1 group mRNA. Results: GemininmRNA in normal cervical tissues, cervical inflammation, CIN grade, CIN grade, CIN grade III expression in the five groups the amount was 0.56 + 0.00,0.48 + 0.10,2.23 + 0.23,3.48 + 0.54,5.07 + 0.28.Cdt1 mRNA expression respectively: 1.11 + 0.00,1.01 + 0.58,2.87 + 1.24,4.09 + 1.64,5.52 + 1.36. with the increase of CIN level, the expression of Geminin and Cdt1 of mRNA increased gradually, and the comparison between groups with the normal group, the cervicitis group had significant difference (P0.05), normal cervical and cervicitis groups were not statistically significant (P0.05). Conclusion: the abnormal expression of cyclin Geminin and Cdt1 mRNA in cervical lesions, and correlated with the lesion degree of positive, said HPV after infection by altering the expression of cell cycle factor and interference of cervical epithelial cell proliferation cycle, and thus the occurrence of intraepithelial neoplasia and cancer, to provide help for the further research of the pathogenesis of HPV cancer, clinical early diagnosis and prediction of cervical lesions may provide biological parameters. In the second part, Geminin and p16, to study differential expression Ki67 in cervical intraepithelial neoplasia and its relationship with HPV: To investigate the Geminin and p16 cell cycle factor, differential expression of Ki67 in cervical lesions, Geminin and p16, the value of Ki67 diagnosis and prediction in cervical lesions, and their correlation with HPV infection. Methods: a total of 210 cases of patients with cervical lesions the object of study (CIN I, II, III group 70 cases each), colposcopy and pathology for regional organizations around the lesion mucosa of 55 cases of chronic inflammation as the inflammation group. Because of myoma of uterus or uterine gland Muscle disease who underwent hysterectomy for cervical tissues in 30 cases of normal control group, preoperative TCT, HPV were negative, 22-65 years old, average 38 + 12.5 years, cervical specimens were pathologically confirmed diagnosis, and had not received chemotherapy, immune and radiation therapy, were drawn with the consent of the patients informed consent, approved by the research ethics committee of Jiangsu Province People's Hospital. Using immunohistochemistry method in normal cervical, cervicitis, CIN I, Geminin CIN and CIN in tissues. The differential expression of p16 and Ki67, load using HC2 method to detect HPV. Results: Geminin, P16 positive or weakly positive expression of.Geminin in CIN I and CIN II in normal cervix and cervicitis tissues, the positive expression in CIN were 12.9%, 54.3%, 92.9% (P0.05); the positive rate of P16 was 15.7%, 61.4%, 87.1% (P0.05).Ki67 in normal cervix and cervicitis tissues were 3.3% and 5.5 % positive expression in CIN I, CIN II, CIN III in 35.7%, 82.9%, 95.7% positive expression (P0.05). With the increased levels of CIN, Geminin and p16, Ki67 expression gradually increased, compared with the normal group and the inflammation group, there were significant differences (P0.05), normal cervical and the inflammation group was not statistically significant (P0.05).HPV in cervicitis, CIN I, CIN II, CIN III tissues were 53.2118.2354.6489.7 median (P0.05).Geminin specificity and positive predictive value of the highest.Geminin, HPV expression and Ki67 infection correlation. Conclusion: the sensitivity of Geminin to the degree of cervical intraepithelial neoplasia the slightly lower than P16, Ki67, but the specificity, the positive predictive value was higher than that of P16, Ki67, and the negative predictive value and accuracy between P16 and Ki67, HPV expression and Geminin infection was positively related to Ki67 and the expression of HPV and p16, and the infection had no correlation. Geminin in the clinical diagnosis of cervical lesions more superiority in cervical lesions can be considered as a new index of cell cycle factor to assist early, accurate diagnosis and prediction of cervical lesions. The third part of the cervical high-grade intraepithelial neoplasia hysterectomy clinical pathological parameters Objective: analysis of cervical high-grade intraepithelial neoplasia patients with hysterectomy, distribution of cervical cytology before operation, load HPV, cervical biopsy and the coincidence rate of colposcopy, cervical conization, and the relationship between cervical lesions and early cone positive margin residual, risk of vaginal stump lesions in and after operation, provide the basis for clinical evaluation of CIN II in patients with hysterectomy and vaginal stump need follow-up. Methods 368 cases with CIN II - III patients with hysterectomy were, respectively from the correlation of cervical cytology, HPV and cervical lesions, Yin The coincidence rate of tract judgment and cervical biopsy, comparison of cervical conization margin positive and hysterectomy pathology, were analyzed in the aspects of vaginal stump after review. Results: all patients TCT examination results in the highest proportion of ASCUS (40.5%), but the difference was not statistically significant between the load between different cytology results of HPV (P0.05). Cervical conization margin positive cases, there is a direct correlation with residual lesions after hysterectomy (P0.05). The vaginal stump VAIN ratio was 11.1% with the incidence. Conclusion: the cervical high-grade intraepithelial neoplasia patients with hysterectomy need to be individualized treatment of vaginal stump up can not be ignored.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R737.33

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