大细胞肺癌中VEGF的表达与DCs Treg分布的相关性研究

Relationship between VEGF Expression and Dendritic Cells and Regulatory T Cell Distribution in Large Cell Lung Cancer

目的:探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)在大细胞肺癌(large cell lung cancer,LCLC)肿瘤组织中的表达及树突状细胞(dendritic cells,DCs)、调节性T细胞(regulatory T cells,Treg)在肿瘤组织和癌旁正常组织中的分布情况,探讨VEGF的表达情况、DCs与Treg的分布情况之间的相关性,及DCs、Treg分布与患者临床特征间的关系。方法:收集天津医科大学附属肿瘤医院自2000年5月至2010年10月手术切除的原发性LCLC标本75例,其中27例癌旁正常组织作为对照。采用免疫组织化学法检测LCLC标本中VEGF的表达、未成熟DC细胞(CD1a^+DC)、成熟DC细胞(CD83^+DC)及Treg细胞(Foxp3^+T细胞)的分布,并分析它们之间的相关性及与患者临床特征的关系。结果:75例癌组织中VEGF的阳性率为94.7%(71/75);CD1a^+DC、CD83^+DC在癌组织中的分布均显著低于癌旁正常组织(P=0.005、P<0.001);Foxp3^+T在癌组织中的分布显著高于癌旁正常组织(P<0.001)。CD83^+DC的分布在VEGF阳性组明显低于VEGF阴性组(χ~2=7.802,P=0.020);CD1a^+DC与Foxp3^+T的分布呈正相关(r_s=0.246,P=0.033)。CD83^+DC的分布在不同T分期间存在差异,随着T分期增高其数量降低(χ~2=11.043,P=0.011)。结论:LCLC组织中VEGF高表达与成熟DC数量的减少相关,而未成熟DC的分布与Treg细胞的分布呈正相关。

Objective： This study aims to investigate the distribution of dendritic cells （DCs） and regulatory T cells （Treg） in human large cell lung cancer （LCLC） patients with different clinical characteristics and to compare the correlation between the expression of vascular endothelial growth factor （VEGF） and the distribution of the two subsets. Methods： Seventy-five cases of LCLC paraffin-embedded tissues treated in Tianjin Cancer Hospital from May 2000 May to November 2010 and 27 cases of normal adjacent tissues were collected. The VEGF expression and the distribution of DCs and Treg were detected using immunohistochemistry. The correlation between the VGEF expression and the distribution of the cells and their clinical features were then analyzed. Results： Positive VEGF expression in LCLC tissues was characterized by brown granules in the cytoplasm of the tumor cells and was detected in 71 （94.7%） patients. Both counts of the CD1 a＋ and CD8T DCs per high-power field in the LCLC tissues were lower compared with those in the adjacent normal tissues （P=-0.005 and P〈0.001, respectively）. The count of Foxp3＋ Treg cells in the tumor tissues was higher than that in the adjacent normal tissues （P〈0.001）. The dis- tribution of CD83＋ DCs in the VEGF-positive group was significantly lower than that in the VEGF-negative group （x2 = 7.802, P =0.020）. A positive correlation was observed between the CDla DCs and Foxp3＋ Treg distribution in LCLC （x2=0.373, P=-0.001）. The high distribution of CD83＋ DCs was related to the small tumor size （ X2=11.043, P=0.011）. Conclusion： VEGF expression affects the mature degree of DCs. Moreover, a positive correlation was observed between the distribution of immature DCs and Treg.