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目的:探讨血管内皮生长因子(VEGF)-C、-D及其受体3(VEGFR-3)在非小细胞肺癌(NSCLC)中的表达规律、与微淋巴管密度(MLVD)、淋巴转移之间的关系及其在NSCLC发生发展、预后中的意义。方法:以40例经病理确诊的NSCLC组织为实验组,以11例肺良性病变组织为对照组,采用免疫组织化学染色法对上述组织中VEGF-C、VEGF-D、VEGFR-3、淋巴管内皮透明质酸受体-1(LYVE-1)、同源异型盒转录因子(Prox-1)蛋白的表达进行分析,并计数微淋巴管密度。结果:①NSCLC组织中VEGF-C、VEGF-D及VEGFR-3蛋白的阳性率分别为77.50%(31/40例)、67.50%(27/40例)、62.50%(25/40例),明显高于肿瘤周边组织(距肿瘤边缘100μm区域内)及肺良性病变组织(P<0.01)。②VEGF-C与VEGFR-3(r=0.409,P=0.005)、VEGF-D与VEGFR-3蛋白表达(r=0.492,P=0.000)均存在相关性;而VEGF-C与VEGF-D蛋白表达无相关性(r=0.256,P=0.093)。③VEGF-C、VEGF-D及VEGFR-3蛋白的表达与NSCLC患者的性别、年龄、肿瘤的大小、组织学类型、分化程度无关,但与肿瘤的淋巴结转移(P<0.05)、PTNM分期(P<0.05)显著相关。④NSCLC肿瘤中心组织中LYVE-1及Prox-1标记的MLVD分别为4.22±1.25、1.99±1.49,明显低于肺良性病变组织(P=0.000),而NSCLC肿瘤周边部位的MLVD显著高于肿瘤中心部位及肺良性病变组织(P=0.000)。VEGF-C、VEGF-D、VEGFR-3表达阳性的组织中,MLVD显著高于阴性组织(P<0.05)。MLVD与肿瘤的淋巴结转移(P=0.000)、PTNM分期(P=0.000)显著相关。结论:淋巴管生成因子VEGF-C、VEGF-D及其受体VEGFR-3蛋白在NSCLC中表达显著增高,并且通过VEGF-C、VEGF-D/VEGFR-3信号通路诱导淋巴管内皮细胞新生和淋巴管生成,从而促进淋巴结转移和肿瘤生长;VEGF-C、VEGF-D及其受体VEGFR-3可能成为检测NSCLC淋巴转移和评估预后的重要分子指标;淋巴管内皮细胞特异性标志物LYVE-1、Prox-1可以较严格地区分血管和淋巴管内皮,相对精确地评价肿瘤的脉管系统。
Objective: To investigate the expression of vascular endothelial growth factor (VEGF) -C, -D and its receptor 3 (VEGFR-3) in non-small cell lung cancer (NSCLC) The relationship between NSCLC and its development and prognosis significance. Methods: Forty NSCLC tissues confirmed by pathology were selected as experimental group and 11 benign lung tissues as control group. Immunohistochemical staining was used to detect the expression of VEGF-C, VEGF-D, VEGFR-3, lymphatic vessels The expression of hyaluronan receptor-1 (LYVE-1), homeobox cassette transcription factor (Prox-1) protein was analyzed and the lymphatic vessel density was counted. Results: ① The positive rates of VEGF-C, VEGF-D and VEGFR-3 in NSCLC were 77.50% (31/40), 67.50% (27/40) and 62.50% (25/40) (P <0.01) higher than the surrounding tissue (within 100 μm from the edge of the tumor) and benign lung lesions. VEGF-C and VEGFR-3 (r = 0.409, P = 0.005), VEGF-D and VEGFR-3 protein expression (r = 0.492, P = 0.000) No correlation (r = 0.256, P = 0.093). The expression of VEGF-C, VEGF-D and VEGFR-3 were not related with the gender, age, tumor size, histological type and differentiation of patients with NSCLC, but with the lymph node metastasis (P <0.05), PTNM stage <0.05) significant correlation. (4) The MLVDs of LYVE-1 and Prox-1 in NSCLC tumor center were 4.22 ± 1.25 and 1.99 ± 1.49, respectively, which were significantly lower than those in benign lung tissues (P = 0.000), while the MLVD in peripheral region of NSCLC was significantly higher than that in tumor center Site and benign lung tissue (P = 0.000). The positive rate of MLVD in VEGF-C, VEGF-D and VEGFR-3 was significantly higher than that in negative tissue (P <0.05). MLVD was significantly associated with lymph node metastasis (P = 0.000) and PTNM stage (P = 0.000). CONCLUSION: The expressions of VEGF-C, VEGF-D and VEGFR-3 are significantly increased in NSCLC, and lymphatic endothelial cell neovascularization is induced by VEGF-C and VEGF-D / VEGFR-3 signaling pathway Lymphangiogenesis and lymph node metastasis and tumor growth; VEGF-C, VEGF-D and its receptor VEGFR-3 may be an important molecular marker for detecting lymph node metastasis and assessing prognosis of NSCLC; lymphatic endothelial cell specific marker LYVE- 1, Prox-1 can be more strict distinction between blood vessels and lymphatic endothelium, relatively accurate evaluation of tumor vasculature.