本文選題：宮頸癌　切入點(diǎn)：宮頸上皮內(nèi)瘤變　出處：《鄭州大學(xué)》2017年碩士論文

【摘要】：背景及目的宮頸癌是造成女性死亡的最常見的婦科惡性腫瘤之一。中國每年新發(fā)病例及死亡人數(shù)在全球居高不下,且發(fā)病率漸呈年輕化趨勢(shì),其浸潤及轉(zhuǎn)移是導(dǎo)致晚期宮頸癌患者死亡的重要原因。尋找宮頸癌在浸潤和轉(zhuǎn)移過程中的敏感指標(biāo)或其發(fā)展中的關(guān)鍵因子,對(duì)提高宮頸癌患者生存率及生存質(zhì)量非常重要。腫瘤的發(fā)生發(fā)展與腫瘤細(xì)胞所在微環(huán)境密切相關(guān),結(jié)合文獻(xiàn)及我們前期的研究結(jié)果顯示,腫瘤相關(guān)成纖維細(xì)胞(tumor-associated fibroblasts,TAFs)為癌細(xì)胞周圍基質(zhì)的主要組成部分,在宮頸癌的惡性轉(zhuǎn)化和進(jìn)展中起著重要作用。成纖維細(xì)胞激活后表達(dá)a-SMA,成為肌纖維母細(xì)胞,即TAFs。a-SMA是成纖維細(xì)胞成為腫瘤基質(zhì)的一個(gè)標(biāo)志。TGF-β1是介導(dǎo)這種相互作用的關(guān)鍵細(xì)胞因子,但其發(fā)生發(fā)展的機(jī)制仍不清楚。已有研究顯示,在乳腺癌、卵巢癌、結(jié)直腸癌等癌癥中,TGF-β1可刺激癌周正常組織成纖維細(xì)胞的CLIC4水平升高,且CLIC4高表達(dá)于癌組織的腫瘤相關(guān)成纖維細(xì)胞。因此推測(cè),CLIC4、TGF-β1和α-SMA在宮頸癌的發(fā)生發(fā)展中發(fā)揮作用,但目前國內(nèi)外關(guān)于CLIC4在宮頸癌中的研究報(bào)道極少。我們采用免疫組織化學(xué)方法檢測(cè)CLIC4、TGF-β1和α-SMA在117例宮頸癌、48例高級(jí)別鱗狀上皮內(nèi)瘤變(HSIL,即CINⅡ~Ⅱ)、28例慢性宮頸炎組織中的表達(dá),并分析其表達(dá)與宮頸癌患者臨床病理特征的關(guān)系以及三者表達(dá)的相關(guān)性,有助于研究宮頸癌細(xì)胞與TAFs之間相互作用原理,從而進(jìn)一步揭示宮頸癌浸潤轉(zhuǎn)移的機(jī)制。材料和方法1.研究對(duì)象:收集鄭州大學(xué)第一附屬醫(yī)院病理標(biāo)本庫2014年1月~2015年1月手術(shù)切除的宮頸癌患者的腫瘤組織117例(所有患者術(shù)前均未進(jìn)行放化療),HSIL患者的宮頸病變組織48例,另選取因非宮頸疾病切除子宮的患者的宮頸組織28例作為對(duì)照,2名有經(jīng)驗(yàn)的病理組織學(xué)專家證實(shí)診斷。117例宮頸癌患者中:年齡29~70歲,中位年齡46歲;FIGO分期(2012年):I期67例,II期50例;組織學(xué)類型:鱗癌99例,腺癌18例;分化程度:G1 64例,G2 27例,G3 26例;間質(zhì)浸潤深度:≤間質(zhì)1/2 82例,間質(zhì)1/2 35例;淋巴結(jié)轉(zhuǎn)移:有21例,無96例.2.實(shí)驗(yàn)方法:免疫組織化學(xué)SP法檢測(cè)3組標(biāo)本中CLIC4,TGF-β1和α-SMA的表達(dá),分析其在3組之間的表達(dá)差異,探究其表達(dá)與臨床病理因素的關(guān)系,并分析三者者之間表達(dá)的相關(guān)性。3.統(tǒng)計(jì)學(xué)分析:應(yīng)用SPSS21.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)處理。陽性率之間的比較應(yīng)用χ~2檢驗(yàn),CLIC4,TGF-β1和α-SMA的表達(dá)相關(guān)性用Spearman等級(jí)相關(guān)分析。P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果1.CLIC4在宮頸癌、CIN和慢性宮頸炎組織中的陽性表達(dá)率分別為76.92%、45.83%和10.71%。宮頸癌組織中CLIC4的表達(dá)率高于CIN和慢性宮頸炎,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。宮頸癌組織中CLIC4的表達(dá)與淋巴結(jié)轉(zhuǎn)移(χ2=4.84,P=0.04)和間質(zhì)浸潤深度(χ2=8.48,P=0.009)、FIGO分期(χ2=8.41,P=0.001)有關(guān),與分化程度(χ2=2.50,P=0.12)、年齡(χ2=0.33,P=0.66)、組織學(xué)類型(χ2=1.08,P=0.37)無關(guān)。2.TGF-β1在宮頸癌組織中的陽性表達(dá)率為70.08%,在HSIL表達(dá)陽性率為47.91%,在慢性宮頸炎組織中為17.85%。宮頸癌組織中TGF-β1的表達(dá)率高于HSIL組織,差異有統(tǒng)計(jì)學(xué)意義(P0.05),宮頸癌組織中TGF-β1的表達(dá)率高于宮頸炎組織,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。宮頸癌組織中TGF-β1的表達(dá)與淋巴結(jié)轉(zhuǎn)移(χ2=5.08,P=0.03)和間質(zhì)浸潤深度(χ2=10.85,P=0.001)、FIGO分期(χ2=8.06,P=0.01)有關(guān),與年齡(χ2=0.03,P=0.60)、分化程度(χ2=2.45,P=0.15)、組織學(xué)類型(χ2=0.60,P=0.58)無關(guān)。3.α-SMA宮頸癌組織中的陽性表達(dá)率為97.43%,在HSIL組織中表達(dá)陽性率為47.91%,在慢性宮頸炎中為7.14%。宮頸癌組織中α-SMA的表達(dá)率高于宮頸上皮內(nèi)瘤變組織,差異有統(tǒng)計(jì)學(xué)意義(P0.05),宮頸癌組織中α-SMA的表達(dá)率高于宮頸炎組織,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。宮頸癌組織中α-SMA的表達(dá)與淋巴結(jié)轉(zhuǎn)移(χ2=14.08,P=0.001)和間質(zhì)浸潤深度(χ2=7.21,P=0.03)有關(guān),與年齡(χ2=0.23,P=0.80)、FIGO分期(χ2=3.52,P=0.12)、組織學(xué)類型(χ2=0.76,P=0.40)、分化程度(χ2=2.30,P=0.26)無關(guān)。4.宮頸癌組織中CLIC4和TGF-β1的表達(dá)存在正相關(guān)(r=0.625,P=0.001);CLIC4和α-SMA的表達(dá)存在正相關(guān)(r=0.624,P=0.001)。結(jié)論1.宮頸癌組織中CLIC4、TGF-β1和α-SMA在宮頸癌組織中存在高表達(dá),隨著宮頸病變的進(jìn)展,CLIC4、TGF-β1和α-SMA的表達(dá)率逐漸升高,提示CLIC4、TGF-β1和α-SMA與宮頸癌的發(fā)生發(fā)展有關(guān)。2.宮頸癌組織中CLIC4和TGF-β1的表達(dá)與宮頸癌淋巴結(jié)轉(zhuǎn)移、間質(zhì)浸潤深度、FIGO分期有關(guān);α-SMA的陽性表達(dá)與宮頸癌淋巴結(jié)轉(zhuǎn)移、間質(zhì)浸潤深度有關(guān)。提示CLIC4、TGF-β1和α-SMA可能與宮頸癌的浸潤和轉(zhuǎn)移有關(guān)。
[Abstract]:Background and objective: cervical cancer is one of the causes of death in women the most common gynecological malignant tumor. China new cases every year and the death toll in the global high, and the incidence rate was gradually younger, its invasion and metastasis is the leading cause of death in patients with advanced cervical cancer. Cervical cancer to find key factors in the invasion and sensitive index in the process of the transfer or in its development, it is very important to improve the survival rate of patients with cervical cancer and quality of life. The occurrence and development of tumor and tumor cells are closely related to the microenvironment, combined with the literature and our previous studies showed that tumor associated fibroblasts (tumor-associated, fibroblasts, TAFs) as the main component of cancer cells around the matrix, which plays an important role in the malignant transformation and progression of cervical cancer. The expression of a-SMA in fibroblasts after activation into myofibroblasts, namely TAFs.a- SMA is the fibroblasts as a sign of.TGF- beta 1 tumor stromal cells are crucial factors mediating this interaction, but its development mechanism is still not clear. Studies have shown that in breast cancer, ovarian cancer, colorectal cancer and other cancers, TGF- beta 1 stimulates cancer Zhou Zheng tissue fibroblast cells with elevated levels of CLIC4, and the high expression of CLIC4 in cancer tissue of tumor associated fibroblasts. It was suggested that CLIC4, TGF- beta 1 and alpha -SMA in cervical cancer play an important role in the development at home and abroad, but the reports about CLIC4 in cervical cancer is less. We detected by immunohistochemical method CLIC4, TGF- beta 1 and alpha -SMA in 117 cases of cervical cancer, 48 cases of high grade squamous intraepithelial neoplasia (HSIL, CIN, 2 ~ 2) expression in 28 cases of chronic cervicitis tissues, and analyze the relationship between the expression and clinicopathological characteristics of patients with cervical cancer as well as the three table As the correlation, are helpful in the study of cervical cancer cells and TAFs interaction principle, so as to further explore the mechanism of invasion and metastasis of cervical cancer. Materials and methods: 1. subjects from the First Affiliated Hospital of Zhengzhou University Library in January January 2014 ~2015 pathological specimens of surgical resection in patients with cervical cancer tumor tissue (117 cases of all patients without chemotherapy), tissues of cervical lesions in patients with HSIL 48 cases were selected for cervical disease non hysterectomy patients of cervical tissue in 28 cases as control, 2 experienced experts in histopathology confirmed the diagnosis of.117 cases of cervical cancer patients: age 29~70 years old, the median age was 46 years; FIGO stage (2012) 67 cases of stage I, 50 stage II cases; squamous cell carcinoma 99 cases, 18 cases of adenocarcinoma; differentiation: G1 64 cases, G2 27 cases, G3 26 cases; 82 cases of interstitial infiltration depth: 1/2 quality, 35 cases of 1/2; lymph node metastasis: 21 No cases, 96 cases of.2. experimental methods: immunohistochemistry SP method in 3 specimens of CLIC4 group, the expression of TGF- beta 1 and alpha -SMA, to analyze the differences in expression between the 3 groups, explore the relationship between their expression and clinical pathological factors, and analysis the correlation of.3. expression between the three statistics are: the application of SPSS21.0 statistical software for statistical processing. Using X ~2 test, the positive rate between CLIC4, the correlation between the expression of TGF- beta 1 and alpha -SMA Spearman using.P0.05 rank correlation analysis for the difference was statistically significant. The expression of 1.CLIC4 in cervical cancer, the positive expression of CIN and chronic cervicitis tissues were respectively 76.92%, 45.83% expression of CLIC4 and 10.71%. in cervical carcinoma was higher than that of CIN and chronic cervicitis, the difference was statistically significant (P0.05). The expression of CLIC4 in cervical carcinoma with lymph node metastasis (2=4.84, P=0.04) and depth of stromal invasion (2=8.48, P=0.009), FIGO Staging (2=8.41, P=0.001), and the degree of differentiation (2=2.50, P=0.12), age (2=0.33, P=0.66), histological type (2=1.08, P=0.37) independent of.2.TGF- beta 1 in cervical carcinoma positive expression rate was 70.08%, the expression rate of HSIL was 47.91%. In chronic cervicitis for the expression of 17.85%. in cervical cancer TGF- beta 1 was higher than that of HSIL group, the difference was statistically significant (P0.05), the expression of TGF- beta 1 is higher than the rate of cervicitis cervical cancer tissues, the difference was statistically significant (P0.05). The expression of TGF- and lymph node metastasis in 1 cervical cancer tissues (x 2=5.08, P=0.03) and depth of stromal invasion (2=10.85, P=0.001), FIGO stage (x 2=8.06, P=0.01), and age (2=0.03, P=0.60), differentiation (2=2.45, P=0.15), histological type (2=0.60, P=0.58) independent of.3. alpha positive expression of -SMA in cervical carcinoma rate 97.43%, the expression in HSIL tissue The positive rate was 47.91% in chronic cervicitis for the expression of 7.14%. in cervical cancer was higher than that of the alpha -SMA cervical intraepithelial neoplasia tissues, the difference was statistically significant (P0.05), the expression of -SMA in cervical cancer was higher than that of alpha cervicitis tissue, the difference was statistically significant (P0.05). The expression of alpha -SMA in cervical cancer with lymph node metastasis (2=14.08, P=0.001) and depth of stromal invasion (2=7.21, P=0.03), and age (2=0.23, P=0.80), FIGO stage (x 2=3.52, P=0.12), histological type (2=0.76, P=0.40), degree of differentiation (2=2.30, P=0.26) had a positive correlation the expression of CLIC4 and TGF- beta 1 independent.4. in cervical cancer tissues (r=0.625, P=0.001); there was a positive correlation between CLIC4 and alpha -SMA (r=0.624, P=0.001). Conclusion CLIC4 1. in cervical carcinoma, TGF- beta 1 and alpha -SMA in cervical cancer in high expression, with the progress of cervical lesions CLIC4, TGF- and alpha -SMA beta 1 The expression rate gradually increased, suggesting that CLIC4, TGF- beta 1 and alpha -SMA and cervical cancer related to the occurrence and development of.2. in cervical cancer CLIC4 and TGF- beta 1 expression and cervical carcinoma with lymph node metastasis, depth of stromal invasion, FIGO staging; alpha -SMA expression and lymph node metastasis in cervical cancer, interstitial the depth of invasion. CLIC4, TGF- beta 1 and alpha -SMA and cervical cancer invasion and metastasis.

【學(xué)位授予單位】：鄭州大學(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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本文編號(hào)：1698157