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子宮內(nèi)膜癌中TTF-1的表達(dá)及臨床意義

發(fā)布時(shí)間:2018-08-04 08:55
【摘要】:【研究背景和目的】子宮內(nèi)膜癌(endometrial cancer,EC)為子宮內(nèi)膜上皮來源的惡性腫瘤,是女性生殖道常見的三大惡性腫瘤之一。根據(jù)臨床、內(nèi)分泌等特征,子宮內(nèi)膜癌一般被分為:I型和Ⅱ型兩種。在世界范圍內(nèi),子宮內(nèi)膜癌的發(fā)病率逐漸增加。相關(guān)數(shù)據(jù)表明:2008年后,我國(guó)發(fā)病率最高的女性生殖系統(tǒng)惡性腫瘤為子宮內(nèi)膜癌。早期子宮內(nèi)膜癌,包括FIGO I、Ⅱ期,其5年生存率達(dá)到90%以上;然而,FIGOⅢ期、Ⅳ期患者的5年存活率僅僅為57%~66%及20%~26%。相關(guān)的基礎(chǔ)實(shí)驗(yàn)研究進(jìn)展表明,多種因素影響到子宮內(nèi)膜癌的發(fā)生、進(jìn)展,包括有不同的癌基因、抑癌基因及轉(zhuǎn)錄信號(hào)等,其構(gòu)成的多種信號(hào)參與了子宮內(nèi)膜癌的傳導(dǎo)途徑。子宮內(nèi)膜癌給女性健康造成了極重大的影響,同時(shí)也增加了經(jīng)濟(jì)負(fù)擔(dān)。臨床中,主要采取以手術(shù)為主的方式治療子宮內(nèi)膜癌,必要時(shí)再結(jié)合一些相關(guān)的輔助措施,如放療、內(nèi)分泌治療等,患者預(yù)后并不理想。改善子宮內(nèi)膜癌患者的預(yù)后:關(guān)鍵的問題是能否早期發(fā)現(xiàn)和早期進(jìn)行及時(shí)有效的治療?因此,明確子宮內(nèi)膜癌的病因及發(fā)病機(jī)制對(duì)臨床中子宮內(nèi)膜癌的靶向治療尤為重要。子宮內(nèi)膜癌組織中甲狀腺轉(zhuǎn)錄因子-1(thyroid transcription factor-1,TTF-1)的表達(dá),國(guó)內(nèi)外已有少量的實(shí)驗(yàn)研究,但各研究的結(jié)論尚不一致,且TTF-1在子宮內(nèi)膜組織中表達(dá)的相關(guān)生物學(xué)機(jī)制仍不清楚。本研究擬采用免疫組織化學(xué)方法,檢測(cè)TTF-1在正常子宮內(nèi)膜、子宮內(nèi)膜增生及子宮內(nèi)膜癌中的表達(dá)水平,探討TTF-1在以上三種不同類型子宮內(nèi)膜組織中的表達(dá)差異,并分析子宮內(nèi)膜癌中TTF-1的表達(dá)與腫瘤臨床病理特征之間的關(guān)系!静牧虾头椒ā窟x取大理大學(xué)附屬醫(yī)院病理科存檔石蠟標(biāo)本73例,時(shí)間在2010年1月~2015年6月之間。其中,正常子宮內(nèi)膜組織11例、子宮內(nèi)膜增生17例、子宮內(nèi)膜癌45例。所有被納入實(shí)驗(yàn)的標(biāo)本,均通過兩位資歷較高的病理醫(yī)師的再次確診,并符合世界衛(wèi)生組織的診斷標(biāo)準(zhǔn)。正常子宮內(nèi)膜作為對(duì)照組,實(shí)驗(yàn)組包括子宮內(nèi)膜增生及子宮內(nèi)膜癌。所有標(biāo)本均取自術(shù)前未經(jīng)過任何放療、化療及手術(shù)治療的患者,但必要的診斷性手術(shù)除外。對(duì)73例標(biāo)本進(jìn)行常規(guī)HE染色及免疫組織化學(xué)法檢測(cè)各病例組織中TTF-1的表達(dá),隨后結(jié)合所選子宮內(nèi)膜癌標(biāo)本的相關(guān)臨床病理信息進(jìn)行數(shù)據(jù)整理及分析討論!窘Y(jié)果】1.基本信息:正常子宮內(nèi)膜11例,年齡范圍25歲至57歲,中位年齡為45歲。子宮內(nèi)膜增生17例,年齡在36歲到56歲之間,中位年齡是46歲。子宮內(nèi)膜癌45例,患者的年齡在31歲到78歲之間,中位年齡為56歲。45例子宮內(nèi)膜癌中,漢族21例、白族14例、其他民族10例;有詳細(xì)月經(jīng)史的26例、不清楚的19例;颊叩囊话闩R床資料無明顯的統(tǒng)計(jì)學(xué)差異(P0.05),即所選病例符合實(shí)驗(yàn)條件。2.臨床病理信息:45例子宮內(nèi)膜癌依據(jù)WHO分級(jí)標(biāo)準(zhǔn)分為:高分化的為25例,中低分化的為20例。參照2014年FIGO分期標(biāo)準(zhǔn)進(jìn)行手術(shù)分期:Ia期子宮內(nèi)膜癌有32例、Ib期及Ib期以上的有13例。在45例子宮內(nèi)膜癌中,肌層浸潤(rùn)深度小于1/2的有35例、肌層浸潤(rùn)深度大于等于1/2的有10例;有脈管轉(zhuǎn)移的2例、無轉(zhuǎn)移的43例。3.免疫組織化學(xué)染色結(jié)果3.1 TTF-1在不同類型子宮內(nèi)膜組織中的表達(dá)正常子宮內(nèi)膜組織、子宮內(nèi)膜增生及子宮內(nèi)膜癌中TTF-1的陽(yáng)性率分別為45%(5/11)、35%(6/17)及16%(7/45)。TTF-1在正常子宮內(nèi)膜與子宮內(nèi)膜癌中的表達(dá),差異有統(tǒng)計(jì)學(xué)意義(P=0.030);正常子宮內(nèi)膜與子宮內(nèi)膜增生中TTF-1的表達(dá),差異無統(tǒng)計(jì)學(xué)意義(P=0.701);同時(shí),TTF-1在子宮內(nèi)膜增生與子宮內(nèi)膜癌中的表達(dá),差異也無統(tǒng)計(jì)學(xué)意義(P=0.089)。45例子宮內(nèi)膜癌中TTF-1的陽(yáng)性率為16%(7/45),其中I型子宮內(nèi)膜癌有33例,陽(yáng)性率18%(6/33);II型子宮內(nèi)膜癌12例,陽(yáng)性率為8%(1/12)。比較了I型和II型子宮內(nèi)膜癌中TTF-1的陽(yáng)性反應(yīng),差異無統(tǒng)計(jì)學(xué)意義,P=0.655。3.2 TTF-1的表達(dá)與子宮內(nèi)膜癌臨床病理特征的關(guān)系實(shí)驗(yàn)結(jié)果表明,TTF-1在高分化子宮內(nèi)膜癌與中分化子宮內(nèi)膜癌中的表達(dá),差異有統(tǒng)計(jì)學(xué)意義(P=0.012)。但子宮內(nèi)膜癌中TTF-1的表達(dá)與患者的年齡(P=0.465)、民族(P=0.826)、手術(shù)分期(P=0.180)、浸潤(rùn)肌層的深度(P=0.660)及有無轉(zhuǎn)移(P=0.290)均無相關(guān)性。【結(jié)論】1.TTF-1在正常子宮內(nèi)膜組織與子宮內(nèi)膜癌中的表達(dá),差異有統(tǒng)計(jì)學(xué)意義,再次提示:TTF-1有可能作為一種相關(guān)的生物學(xué)因子,參與了子宮內(nèi)膜癌的發(fā)生及進(jìn)展過程。2.高分化與中分化子宮內(nèi)膜癌中TTF-1的表達(dá)差異有統(tǒng)計(jì)學(xué)意義,提示:在臨床中,TTF-1有可能與子宮內(nèi)膜癌惡性程度的判斷、臨床手術(shù)分期及預(yù)后判斷有一定的關(guān)系。3.一定比例的子宮內(nèi)膜癌表達(dá)TTF-1,當(dāng)原發(fā)部位不明的腫瘤中出現(xiàn)TTF-1陽(yáng)性時(shí),臨床醫(yī)師需要鑒別腫瘤是否為子宮內(nèi)膜癌來源。
[Abstract]:[background and purpose] endometrial cancer (EC) is a malignant tumor of the endometrium epithelium. It is one of the three common malignant tumors in the female genital tract. According to the clinical and endocrine characteristics, endometrial carcinoma is divided into two types: I and type II. In the world, the incidence of endometrial cancer is increasing. Additional data suggest that after 2008, the highest incidence of female genital malignancies in China is endometrial cancer. Early endometrial cancer, including FIGO I, stage II, has a 5 year survival rate of more than 90%; however, the 5 year survival rate of the FIGO III and stage IV patients is only 57% ~66% and 20%~26%. related basic experimental research progress. The factors affect the occurrence and progress of endometrial cancer, including different oncogenes, tumor suppressor genes and transcriptional signals, which constitute a variety of signals involved in the transmission of endometrial cancer. Endometrial cancer has a great impact on women's health and also increased the economic burden. In clinical, mainly by surgery. The treatment of endometrial carcinoma should be combined with some related auxiliary measures, such as radiotherapy, endocrine therapy, and so on. The prognosis of the patients is not ideal. The prognosis of the patients with endometrial cancer is improved: the key problem is whether early detection and early and effective treatment can be carried out. Therefore, the etiology and pathogenesis of endometrial cancer are clear. The target therapy of endometrial carcinoma in the bed is particularly important. The expression of -1 (thyroid transcription factor-1, TTF-1) in endometrial carcinoma has been studied at home and abroad, but the conclusions of each study are not consistent, and the related biological mechanism of TTF-1 in endometrial tissue is still not clear. The expression of TTF-1 in normal endometrium, endometrium hyperplasia and endometrial carcinoma was detected by immunohistochemical method, and the expression of TTF-1 in the three different types of endometrium was investigated. The relationship between the expression of TTF-1 in endometrial carcinoma and the clinicopathological features of the tumor was analyzed. 73 cases of paraffin specimens in the pathology department of the Affiliated Hospital of Dali University were selected, between 11 cases of normal endometrium, 17 cases of endometrial hyperplasia and 45 cases of endometrial carcinoma. All the specimens were confirmed by two senior pathologists and met the health of the world. The diagnostic standard of tissue. Normal endometrium was used as a control group. The experimental group included endometrial hyperplasia and endometrial cancer. All specimens were taken from patients without any radiotherapy, chemotherapy and surgical treatment before operation, except for the necessary diagnostic procedures. 73 specimens were examined by routine HE staining and immunohistochemical staining in each case group. The expression of TTF-1 in the fabric was then combined with the related clinicopathological information of selected endometrium cancer specimens. [results] 1. basic information: 11 cases of normal endometrium, age range from 25 to 57 years, 45 years of age, 17 cases of endometrial hyperplasia, between 36 and 56 years old, the middle age is 46 years old. 45 cases of endometrial carcinoma were aged from 31 to 78 years old, with a median age of 56 years of.45 endometrial carcinoma, 21 Han, 14 and 10 other nationalities, 26 cases with detailed menstrual history and 19 cases that were not clear. The patient's general clinical data had no significant statistical difference (P0.05), that is, the selected cases conformed to the.2. clinicopathological letter of experimental conditions. 45 cases of endometrial carcinoma were divided into 25 cases of high differentiation and 20 cases of middle and low differentiation according to the WHO classification standard. 32 cases of endometrial carcinoma in Ia stage, 13 cases in Ib stage and above Ib stage. In 45 cases of endometrial carcinoma, 35 cases of myometrium infiltration depth is less than 1/2, and the depth of myometrium infiltration is greater than that in 45 cases. There were 10 cases of 1/2, 2 cases with vascular metastasis and 43 cases of non metastatic.3. immunohistochemical staining. 3.1 TTF-1 expressed normal endometrium in different types of endometrium. The positive rate of TTF-1 in endometrium hyperplasia and endometrial carcinoma was 45% (5/11), 35% (6/17) and 16% (7/45).TTF-1 in normal endometrium and children. There was significant difference in the expression of endometrial carcinoma (P=0.030), and there was no significant difference in the expression of TTF-1 in normal endometrium and endometrium hyperplasia (P=0.701); meanwhile, there was no significant difference in the expression of TTF-1 in endometrial hyperplasia and endometrial carcinoma (P=0.089) (P=0.089) the positive rate of TTF-1 in endometrial carcinoma was 16% (7). /45), among them, there were 33 cases of type I endometrial carcinoma, the positive rate was 18% (6/33), and 12 cases of II type endometrial carcinoma, the positive rate was 8% (1/12). The positive reaction of TTF-1 in I and II endometrial carcinoma was compared. The relationship between the expression of P=0.655.3.2 TTF-1 and the clinicopathological features of endometrial carcinoma showed that TTF-1 was in high differentiation. There were significant differences in the expression of endometrial carcinoma and medium differentiated endometrial carcinoma (P=0.012), but there was no correlation between the expression of TTF-1 in endometrial carcinoma and the patient's age (P=0.465), the nationality (P=0.826), the surgical staging (P=0.180), the depth of the infiltrating myometrium (P=0.660) and the metastasis (P=0.290). [Conclusion] 1.TTF-1 is in the normal uterus. The expression of membrane tissue and endometrial carcinoma has a significant difference. Again, it is suggested that TTF-1 may be a related biological factor, involved in the development and progression of endometrial carcinoma, and the difference of TTF-1 expression in.2. highly differentiated and moderately differentiated endometrial carcinoma is of great significance. It is suggested that in clinical, TTF-1 may be associated with the child. The judgment of the malignant degree of endometrial carcinoma, the clinical operation stage and the prognosis have certain relation with the expression of.3. in a certain proportion of endometrial carcinoma. When the TTF-1 is positive in the unidentified tumor, the clinician needs to identify whether the tumor is a source of endometrial cancer.
【學(xué)位授予單位】:大理大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R737.33

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