非小细胞肺癌微血管构筑立体表型异质性评估及意义  

Evaluation of three-dimensional tumor microvascular architecture phenotype heterogeneity in non-small cell carcinoma and its significance

作　　者：周晖[1] 刘进康[1] 陈胜喜[2] 熊曾[1] 周建华[3] 童时宇[4] 陈浩[1] 周漠玲[1] 

机构地区：[1]中南大学湘雅医院放射科,长沙410008 [2]中南大学湘雅医院心胸外科,长沙410008 [3]中南大学湘雅医院病理科,长沙410008 [4]中南大学湘雅医院临床医学八年制,长沙410008

出　　处：《中南大学学报（医学版）》2012年第6期555-560,共6页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(07JJ5010,10JJ5028)~~

摘　　要：目的:探讨非小细胞肺癌(non-small cell carcinoma,NSCLC)微血管构筑立体表型异质性(three-dimensionaltumor microvascular architecture phenotype heterogeneity,3D-TMAPH)的程度、产生机制及其意义。方法:完整地采集21例肺内单发结节标本,每个结节各取5个组织层面,石蜡包埋后构建微血管构筑立体二维表型和立体表型,检测指标包括血管内皮生长因子(vascular endothelial growth factor,VEGF)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、EphB4、ephfinB2的表达及CD34标记的微血管密度(microvascular density,MVD)。用变异系数与异质率来定量评价3D-TMAPH的大小,运用Spearman相关分析探讨3D-TMAPH与NSCLC临床病理特征及微血管构筑二维表型的关系。结果:3D-TMAPH表现为微血管构筑二维表型在NSCLC组织中呈异质性表达,这种异质性存在于形态、类型、数目、二维和立体分布等指标上,恶性结节异质性明显大于结核与活动性炎性病变;NSCLC组织CD34-MVD与PCNA呈现程度不同的异质性,CD34-MVD和PCNA的变异系数与分化程度呈正相关(均P<0.05),与P-TNM分期、组织学类型、淋巴结转移无明显关系(均P>0.05)。不同NSCLC组织中不同表达物(ephrinB2,EphB4,VEGF)异质率不同,但不同病理组织类型的非小细胞肺癌异质率差异无统计学意义(P>0.05)。结论:3D-TMAPH普遍存在于NSCLC发生、发展过程的微环境中,并密切影响NSCLC复杂的生物学特性。Objective： To explore the degree, mechanism and clinical significance of three-dimensional tumor microvascular architecture phenotype heterogeneity （3D-TMAPH） in non-small cell carcinoma （NSCLC）. Methods： Twenty-one samples of solitary pulmonary nodules were collected integrally. To establish two-dimensional tumor microvascular architecture phenotype （2D-TMAP） and three-dimensional tumor microvascular architecture phenotype （3D-TMAP）, five layers of each nodule were selected and embedded in paraffin. Test indices included the expressions of vascular endothelial growth factor （VEGF）, proliferating cell nuclear antigen （PCNA）, EphB4, ephfinB2 and microvascular density marked by anti-CD34 （CD34-MVD）. The degrees of 3D-TMAPH were evaluated by the coefficient of variation and extend of heterogeneity. Spearman rank correlation analysis was used to investigate the relationships between 2D-TMAP, 3D-TMAP and clinicopathological features. Results＂ 3D-TMAPH showed that 2D-TMAP heterogeneity was expressed in the tissues of NSCLC. The heterogeneities in the malignant nodules were significantly higher than those in the active inflammatory nodules and tubercular nodules. In addition, different degrees of heterogeneity of CD34-MVD and PCNA were found in NSCLC tissues. The coefficients of variation of CD34- MVD and PCNA were positively related to the degree of differentiation （all P〈0.0S）, but not related to the P-TNM stages, histological type or lymphatic metastasis （all P〉0.0S）. The level of heterogeneity of various expression indexes （ephrinB2, EphB4, VEGF） in NSCLC tissues were inconsistent, but there were no significant differences in heterogeneity in NSCLC tissues with different histological types （P〉0.05）. Conclusion- 3D-TMAPH exists widely in the microenvironment during the genesis and development of NSCLC and has a significant impact on its biological complexity.

关 键 词：非小细胞肺癌 微血管构筑表型 异质性 

分 类 号：R734.2[医药卫生—肿瘤]