肺原位腺癌、微浸润腺癌及浸润性腺癌中淋巴管密度的变化及其调控因子

Changes of lymphatic vessel density in lung adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma and the regulatory factors

目的分析肺原位腺癌、微浸润腺癌及浸润性腺癌中肿瘤淋巴管密度的变化及其可能的调控因子。方法收集具有完整临床病理资料的肺腺癌病例301例并分为原位腺癌(n=28,9.3%)、微浸润腺癌(n=86,28.6%)及浸润性腺癌(n=187,62.1%)3组。应用D2-40免疫组化标记计数各组肺腺癌中淋巴管密度,同时检测MT1-MMP、VEGF-C蛋白表达水平。分析肺腺癌3种病理类型病例中淋巴管密度的变化差异及其与MT1-MMP、VEGF-C蛋白表达、临床病理因子(特征)的关系。结果淋巴管密度在分析肺原位腺癌、微浸润腺癌及浸润性腺癌组中的变化差异具有统计学意义(P=0.000);淋巴管密度与VEGF-C蛋白表达水平具有相关性(r=0.917, P=0.009)。淋巴管密度与肿瘤大小(r=0.686, P=0.017)、淋巴结转移(r=0.739, P=0.000)及临床分期(r=0.874, P=0.012)具有相关性。结论肿瘤淋巴管生成可能与肺腺癌进展过程和临床病理因子(特征)密切相关,VEGF-C可能是促进肿瘤淋巴管生成的调控因子。

Objective To analyze the changes in tumor lymphatic vessel density(LVD) in patients with lung adenocarcinoma in situ(AIS), minimally invasive adenocarcinoma(MIA), and invasive adenocarcinoma(IA) and explore the regulatory factors of LVD. Methods Complete clinicopathological data were collected form a total of 301 patients with lung adenocarcinoma,including 28(9.3%) with AIS, 86(28.6%) with MIA, and 187(62.1%) with IA. The LVD of all the adenocarcinomas were calculated after D2-40 immunohistochemical staining, and MT1-MMP and VEGF-C expression levels were also evaluated. The differences in LVD among the groups and the correlations of tumor LVD with the expressions of MT1-MMP and VEGF-C and the clinicopathological factors were analyzed. Results The LVD differed significantly among AIS, MIA, and IA groups(P=0.000). The LVDs was significantly correlated with the level of VEGF-C protein expression(r=0.917, P=0.009), tumor size(r=0.686, P=0.017), lymph node metastasis(r=0.739, P=0.000), and clinical stage(r=0.874, P=0.012) of the patients. Conclusions Tumor lymphangiogenesis plays an important role in lung adenocarcinoma progression, and VEGF-C may promote this process.