【摘要】：背景及目的:食管癌是嚴(yán)重威脅我國(guó)人民健康的消化道惡性腫瘤,近年來(lái)發(fā)病率居高不下,據(jù)國(guó)家癌癥中心報(bào)道,2010年我國(guó)食管癌新發(fā)病例高達(dá)287632例,其中90%是食管鱗狀細(xì)胞癌[1]。浸潤(rùn)深度、淋巴結(jié)轉(zhuǎn)移等被認(rèn)為是判斷食管癌患者臨床分期及預(yù)后的關(guān)鍵因素,但是大量的研究報(bào)道淋巴結(jié)轉(zhuǎn)移陰性的患者術(shù)后仍有復(fù)發(fā),推測(cè)淋巴管浸潤(rùn)是復(fù)發(fā)的元兇,因此尋找與淋巴結(jié)轉(zhuǎn)移特別是與淋巴管浸潤(rùn)的相關(guān)因子,對(duì)減少?gòu)?fù)發(fā)提高患者生存率有重大意義。有研究表明VEGF-C能夠促進(jìn)多種腫瘤細(xì)胞的增殖、生長(zhǎng)、侵襲轉(zhuǎn)移及腫瘤微淋巴管生成,CTTN蛋白與癌細(xì)胞運(yùn)動(dòng)、侵襲及抗失巢凋亡能力有關(guān)。但是目前國(guó)內(nèi)尚缺乏關(guān)于VEGF-C和CTTN與食管鱗癌浸潤(rùn)深度、淋巴管浸潤(rùn)和淋巴結(jié)轉(zhuǎn)移等病理特征關(guān)系及預(yù)測(cè)預(yù)后的的研究。本實(shí)驗(yàn)通過(guò)免疫組化的方法分析VEGF-C、CTTN在食管鱗癌組織中的表達(dá)及D2-40標(biāo)記的食管鱗癌淋巴管浸潤(rùn)(LVI)與食管鱗癌臨床病理特征和預(yù)后的關(guān)系。方法:采用免疫組織化學(xué)法檢測(cè)216例食管鱗癌和癌旁正常食管黏膜組織中VEGF-C和CTTN蛋白表達(dá)及D2-40標(biāo)記的淋巴管浸潤(rùn)(LVI)的情況,應(yīng)用SPSS19.0軟件分析其與食管鱗癌臨床病理特征之間的關(guān)系,隨訪觀察患者總生存期。結(jié)果:VEGF-C、CTTN在食管鱗癌和癌旁正常食管黏膜組織中的陽(yáng)性表達(dá)率分別為43.1%、63.9%和10.6%、25.5%,兩者差異有統(tǒng)計(jì)學(xué)意義(P=0.000);216例食管鱗癌患者淋巴管浸潤(rùn)率為63.9%。食管鱗癌浸潤(rùn)深度(p T)、TNM分期、淋巴結(jié)轉(zhuǎn)移(pN)和淋巴管浸潤(rùn)(LVI)與食管鱗癌組織中VEGF-C、CTTN的表達(dá)相關(guān),差異均有統(tǒng)計(jì)學(xué)意義(P0.001)。Logistic單因素和多因素回歸分析均顯示VEGF-C、CTTN、LVI和TNM分期是預(yù)測(cè)淋巴結(jié)轉(zhuǎn)移的獨(dú)立影響因素(P=0.001,P=0.006,P=0.004,P=0.003);而在單因素分析中浸潤(rùn)深度是影響淋巴結(jié)轉(zhuǎn)移的獨(dú)立因素(P=0.042),但多因素分析中浸潤(rùn)深度不能成為預(yù)測(cè)淋巴結(jié)轉(zhuǎn)移的獨(dú)立危險(xiǎn)因素。Kaplan-Meier生存分析顯示VEGF-C(-)組的中位生存時(shí)間51.0個(gè)月,高于VEGF-C(+)組的中位生存時(shí)間28.0個(gè)月;CTTN(-)組的中位生存時(shí)間54.0個(gè)月,顯著高于CTTN(+)組的中位生存時(shí)間26.0個(gè)月;VEGF-C和CTTN的Log rank值分別為11.810、18.100,上述差異均有統(tǒng)計(jì)學(xué)意義(P0.001)。同時(shí)Kaplan-Meier生存分析顯示LVI(+)組中位生存時(shí)間26.0個(gè)月(95%CI:16.843~35.157個(gè)月)明顯低于LVI(-)組的中位生存時(shí)間54.0個(gè)月(95%CI:39.467~568.533個(gè)月),差異有統(tǒng)計(jì)學(xué)意義(P0.001)。Cox多因素分析示浸潤(rùn)深度pT、TNM分期、LVI、pN、VEGF-C、CTTN為影響食管鱗癌預(yù)后的獨(dú)立影響因素差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:VEGF-C、CTTN有望成為食管鱗癌預(yù)測(cè)病理分期、淋巴管浸潤(rùn)、淋巴結(jié)轉(zhuǎn)移及預(yù)后方面可靠的腫瘤標(biāo)志物。
[Abstract]:Background and objective: esophageal cancer is a malignant tumor of digestive tract that threatens the health of Chinese people. The incidence of esophageal cancer is high in recent years. According to the report of the National Cancer Center, the number of new cases of esophageal cancer in China in 2010 was as high as 287632 cases. 90% of them were squamous cell carcinoma of the esophagus. The depth of invasion and lymph node metastasis are considered to be the key factors to judge the clinical stage and prognosis of patients with esophageal cancer. However, a large number of studies have reported that the patients with negative lymph node metastasis still have recurrence after operation, and it is assumed that lymphatic invasion is the main cause of recurrence. Therefore, it is of great significance to search for factors related to lymph node metastasis, especially lymphatic invasion, to reduce recurrence and improve survival rate. Some studies have shown that VEGF-C can promote the proliferation, growth, invasion and metastasis of many kinds of tumor cells and tumor microlymphangiogenesis. CTTN protein is related to the ability of cancer cell movement, invasion and anti-nesting and apoptosis. However, there is still a lack of research on the relationship between VEGF-C and CTTN and the depth of invasion, lymphatic invasion and lymph node metastasis in esophageal squamous cell carcinoma and prognosis. The expression of VEGF-C,CTTN in esophageal squamous cell carcinoma and the relationship between D2-40 labeled lymphatic infiltrating (LVI) and clinicopathological features and prognosis of esophageal squamous cell carcinoma were analyzed by immunohistochemical method. Methods: immunohistochemical method was used to detect the expression of VEGF-C and CTTN protein and D2-40 labeled lymphatic infiltrating (LVI) in 216 cases of esophageal squamous cell carcinoma and adjacent normal esophageal mucosa. SPSS19.0 software was used to analyze the relationship between the clinicopathological features of esophageal squamous cell carcinoma and the total survival time. Results: the positive expression rates of VEGF-C,CTTN in esophageal squamous cell carcinoma and adjacent normal esophageal mucosa were 43.9% and 10.625. 5%, respectively. The difference between them was statistically significant (P < 0. 000). The lymphatic infiltration rate in 216 cases of esophageal squamous cell carcinoma was 63.9%. The expression of VEGF-C,CTTN in esophageal squamous cell carcinoma was correlated with (p T), TNM stage of invasive depth of esophageal squamous cell carcinoma, (pN) of lymph node metastasis and (LVI) of lymphatic invasion. The difference was statistically significant (P0. 001). Logistic univariate and multivariate regression analysis showed that VEGF-C,CTTN,LVI and TNM staging were independent factors in predicting lymph node metastasis (P0. 001). In univariate analysis, the depth of invasion was an independent factor affecting lymph node metastasis (P0. 042). However, the depth of invasion in multivariate analysis was not an independent risk factor for predicting lymph node metastasis. Kaplan-Meier survival analysis showed that the median survival time of VEGF-C (-) group was 51.0 months. The median survival time was 28.0 months higher than that in VEGF-C () group. The median survival time of CTTN (-) group was 54.0 months, which was significantly higher than that of CTTN () group (26.0 months), and the Log rank values of VEGF-C and CTTN were 11.810 鹵18.100, respectively. The above differences were statistically significant (P0.001). Meanwhile, Kaplan-Meier survival analysis showed that the median survival time of LVI () group was 26.0 months (95 CI: 16.843 ~ 35.157 months), which was significantly lower than that of LVI (-) group (95 CI: 39.467-568.533 months). The difference was statistically significant (P0. 001). Cox multivariate analysis showed that the invasive depth of pT,TNM staging, LVI,pN,VEGF-C,CTTN as an independent factor affecting the prognosis of esophageal squamous cell carcinoma, there was no significant difference (P0.05). Conclusion: VEGF-C,CTTN may be a reliable tumor marker for predicting pathological stage, lymphatic invasion, lymph node metastasis and prognosis of esophageal squamous cell carcinoma.
【學(xué)位授予單位】：承德醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.1

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