LYVE-1、Prox-1在非小细胞肺癌中的表达及其与淋巴转移的关系

Expression of LYVE-1 and Prox-1 in Non-small Cell Lung Cancer and the Relationship with Lymph Node Metastasis

目的探讨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)在非小细胞肺癌(NSCLC)中的表达规律,与微淋巴管密度(MLVD)及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(分为肿瘤中心组织及肿瘤周边组织)为实验组,以11例肺良性病变组织为对照组,采用免疫组化法检测上述组织中LYVE-1、Prox-1及CD31蛋白的表达,光镜下计数MLVD及微血管密度。结果①NSCLC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,低于肺良性病变组织(P均为0.000)。②NSCLC肿瘤周边组织中LYVE-1及Prox-1标记的MLVD分别为10.89±2.06、6.63±1.99,高于肿瘤中心部位及肺良性病变组织(P均为0.000)。③肿瘤周边组织中LYVE-1及Prox-1标记的MLVD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,但在有无肿瘤的淋巴结转移(P=0.000)、PTNM分期的高低间(P=0.000)差异有统计学意义,且随着肿瘤的淋巴结转移、PTNM分期的升高,LYVE-1及Prox-1蛋白的表达量及MLVD增加。而CD31与肿瘤的淋巴结转移、PTNM分期无关。④LYVE-1与Prox-1标记的MLVD相关(r=0.529,P=0.000)。LYVE-1、Prox-1标记的MLVD与CD31标记的微血管密度无关。结论与肿瘤淋巴转移相关的有功能的淋巴管主要位于肿瘤周边部位,而非肿瘤中心部位;LYVE-1与Prox-1可能成为检测NSCLC淋巴转移和评估预后的重要分子指标。

Objective To investigate the expression of lymphatic vessel endothelial hyaluronan receptor-1（LYVE-1）,the homeobox gene（Prox-1）,in patients with non-small cell lung cancer（NSCLC）,the relationship with microlymphatic vessel density,lymph node metastasis and their clinic pathological value.Methods Forty specimens of the NSCLC as experimental group and eleven pulmonary benign diseases as control group were studied.The expressions of LYVE-1,Prox-1 and CD31 protein in specimens of NSCLC and normal pulmonary tissue were studied with immunohistochemical（IHC） technique.Microlymphatic vessel density（MLVD） and microvessel density（MVD） were counted.Meanwhile,all specimens were also examined by conventional pathological method.Clinicopathological data of each patient were recorded and analyzed.Results ①Among 40 cases of the center of NSCLC cancerous tissues,the MLVDs marked by LYVE-1 and Prox-1 were 4.22±1.25 and 1.99±1.49 respectively,which were significantly lower than those of the pulmonary benign diseases tissues（P=0.000）.②The MLVDs marked by LYVE-1 and Prox-1 in NSCLC cancerous invasive edge were 10.89±2.06 and 6.63±1.99 respectively,which were significantly higher than those in the center of cancerous tissues and those of the pulmonary benign diseases tissues（P=0.000）.③The MLVDs marked by LYVE-1 and Prox-1 in cancerous invasive edge were not correlated with age,gender,site and dimension of lesion,types of histological and degree of differentiation,but correlated significantly with lymph node metastasis（P=0.000） and PTNM stage（P=0.000）.Meanwhile,along with lymph node metastasis and increasing of PTNM stage,the expressions of LYVE-1 and Prox-1 protein and MLVDs have significantly increased,but the microvessel density marked by CD31 in cancerous invasive edge was not correlated significantly with lymph node metastasis（P=0.450） and PTNM stage（P=0.377）.④Significantcorrelation between LYVE-1 and Prox-1（r=0.529,P=0.000） expression was observed in NSCLC;moreover,no correlations between LYVE-1 and CD31,Prox-1 and CD31 （r=0.034,P=0.837;r=-0.075,P=0.647） were observed.ConclusionThe functional microlymphatic vessels correlated with lymphatic metastasis are mainly located in the cancerous invasive edge rather than the center of cancerous tissues.LYVE-1 and Prox-1 might be acted as molecular phenotypes of lymphangioghesis in NSCLC and as important markers for evaluating lymphatic metastasis and prognosis in patients with NSCLC.