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

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 P0.05),but not related to the P-TNM stages,histological type or lymphatic metastasis(all P0.05).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(P0.05). Conclusion: 3D-TMAPH exists widely in the microenvironment during the genesis and development of NSCLC and has a significant impact on its biological complexity.