食管鳞癌组织中VEGF-C、CTTN的表达及其临床意义

发布时间：2018-11-01 12:39

【摘要】：背景及目的:食管癌是严重威胁我国人民健康的消化道恶性肿瘤,近年来发病率居高不下,据国家癌症中心报道,2010年我国食管癌新发病例高达287632例,其中90%是食管鳞状细胞癌[1]。浸润深度、淋巴结转移等被认为是判断食管癌患者临床分期及预后的关键因素,但是大量的研究报道淋巴结转移阴性的患者术后仍有复发,推测淋巴管浸润是复发的元凶,因此寻找与淋巴结转移特别是与淋巴管浸润的相关因子,对减少复发提高患者生存率有重大意义。有研究表明VEGF-C能够促进多种肿瘤细胞的增殖、生长、侵袭转移及肿瘤微淋巴管生成,CTTN蛋白与癌细胞运动、侵袭及抗失巢凋亡能力有关。但是目前国内尚缺乏关于VEGF-C和CTTN与食管鳞癌浸润深度、淋巴管浸润和淋巴结转移等病理特征关系及预测预后的的研究。本实验通过免疫组化的方法分析VEGF-C、CTTN在食管鳞癌组织中的表达及D2-40标记的食管鳞癌淋巴管浸润(LVI)与食管鳞癌临床病理特征和预后的关系。方法:采用免疫组织化学法检测216例食管鳞癌和癌旁正常食管黏膜组织中VEGF-C和CTTN蛋白表达及D2-40标记的淋巴管浸润(LVI)的情况,应用SPSS19.0软件分析其与食管鳞癌临床病理特征之间的关系,随访观察患者总生存期。结果:VEGF-C、CTTN在食管鳞癌和癌旁正常食管黏膜组织中的阳性表达率分别为43.1%、63.9%和10.6%、25.5%,两者差异有统计学意义(P=0.000);216例食管鳞癌患者淋巴管浸润率为63.9%。食管鳞癌浸润深度(p T)、TNM分期、淋巴结转移(pN)和淋巴管浸润(LVI)与食管鳞癌组织中VEGF-C、CTTN的表达相关,差异均有统计学意义(P0.001)。Logistic单因素和多因素回归分析均显示VEGF-C、CTTN、LVI和TNM分期是预测淋巴结转移的独立影响因素(P=0.001,P=0.006,P=0.004,P=0.003);而在单因素分析中浸润深度是影响淋巴结转移的独立因素(P=0.042),但多因素分析中浸润深度不能成为预测淋巴结转移的独立危险因素。Kaplan-Meier生存分析显示VEGF-C(-)组的中位生存时间51.0个月,高于VEGF-C(+)组的中位生存时间28.0个月;CTTN(-)组的中位生存时间54.0个月,显著高于CTTN(+)组的中位生存时间26.0个月;VEGF-C和CTTN的Log rank值分别为11.810、18.100,上述差异均有统计学意义(P0.001)。同时Kaplan-Meier生存分析显示LVI(+)组中位生存时间26.0个月(95%CI:16.843~35.157个月)明显低于LVI(-)组的中位生存时间54.0个月(95%CI:39.467~568.533个月),差异有统计学意义(P0.001)。Cox多因素分析示浸润深度pT、TNM分期、LVI、pN、VEGF-C、CTTN为影响食管鳞癌预后的独立影响因素差异无统计学意义(P0.05)。结论:VEGF-C、CTTN有望成为食管鳞癌预测病理分期、淋巴管浸润、淋巴结转移及预后方面可靠的肿瘤标志物。
[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 卤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.
【学位授予单位】：承德医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.1

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