Study On The Relationship Between The Tumor Microvascular Architecture Phenotype Heterogeneity And The MSCT Pulmonary Perfusion Imaging In Non-Small Cell Lung Cancer

Objective To discuss the impact of three-dimensional tumor microvascular architecture phenotype heterogeneity(3D-TMAPH)on the MSCT pulmonary perfusion by constructing a technology platform of two-dimensional tumor microvascular architecture phenotype(2D-TAMP) expression,and explain the mechanism of MSCT pulmonary perfusion in SPN's differential diagnosis and judging the degree of malignancy.Methods 65 patients who were examined in the Thoracic Surgery department of xiangya hospital between 2005 December to 2008 January were underwent CT perfusion scan by 16-slice spiral CT.Among these patients,34 cases were bring into our research after surgery.The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected.The techniques of immunohistochemical staining and special staining and electron microscope observation were performed to build a technology platform of 2D-TMAP expression by dectecting these indexes which including the morphology and the integrity of basement membrane of microvasculature, microvascular density(MVD),various microvascular subtype,the degree of the maturity and lumenization of microvasculature,the characteristics of immunogenetics of microvasculature and so on.Among these 34 cases,the whole specimens of 21 cases'SPN were got and cut into many layers paralleling the corresponding biggest tumor tissue specimens layer of CT perfusion scan in fixed Interval.Five layers were selected.Every layer's 2D-TMAP was detected.Coefficient of variation(CV)and heterogeneity rate were used to evaluate 3D-TMAP.Multiple correlation analysis was used to study the relationship among clinical pathological features,T-MAPand CT perfusion parameters.How 3D-TMAPH exercised influence on CT perfusion mechanisms could be studied at the same time.Resluts:(1)The technology platform of 2D-TMAP expression was constructed successfully.The MVD of surrounding zone and central zone and the total MVD were significantly higher than the MVD of junctional zone(P＜0.05).The MVD of surrounding zone is higher than that of the central zone,but the difference was not statistically significant. With the enlargement of the volume of the nodules,the heterogeneity of MVD increased.The inmplete lumen MVD in the surrounding zone was significantly higher than that of the central area(P＜0.05).EphrinB2 and EphB4 expressed consistently in tumor parenchyma but differently in vascular.(2)The relationship between 2D-TMAP and the clinicopathological character of NSCLC showed that:the CD34-MVD of the surrounding area with the various degree of the maturity of microvascular lumen were positively correlated with the degree of differentiation and lymphatic metastasis(P＜0.05),not correlated to P-TNM staging and histological type of NSCLC(P＞0.05),positively correlated with of the positive rates of PCNA(P＜0.05),and also positively correlated with the expression intensity of VEGF and ephrinB2 and EphB4,respectively(P＜0.05);The degree of differentiation was positively correlated with the positive rates of PCNA and the expression intensity of VEGF and lymphatic metastasis,respectively(P＜0.05),negatively correlated with and the integrity of basement membrane of microvasculature(P＜0.05); The lymphatic metastasis were positively correlated with P-TNM staging and degree of differentiation and the positive rates of PCNA, respectively(P＜0.05),and also positively correlated with the expression intensity of ephrinB2 and EphB4,respectively(P＜0.05).(3)Results of 3D-TMAPH:All of the specimens showed different degrees the heterogeneity of 2D-TMAP and 3D-TMAP,the heterogeneity of normal tissues and inactive inflammatory lesions is less than malignant lesions significantly.The CV of CD34-MVD in NSCLC was distributed between 16.7%and 28.3%,the total CV was 23%.The CV of PCNA in NSCLC was distributed between 4.07%and 8.33%,the total CV was 6.45%.The CV of CD34-MVD(r=0.668,P=0.003)and PCNA(r= 0.535,P=0.02)were positively correlated with the degree of differentiation,respectively;and the overall heterogeneity rates of ephrinB2 and EphB4 and VEGF were 39%,33%,40%,respectively. Adenocarcinoma had the highest rate of heterogeneity(42%),followed by adenosquamous carcinoma(28%),precancerous lesions and squamous cell carcinoma had the lowest rates of heterogeneity(16%～20%).(4)The relationship among the MSCT morphological features and 2d-TMAP and the clinicopathological characters of NSCLC showed that: degree of differentiation had positive correlation with vacuolar sign showed(P＜0.05);PTNM staging had significant positive correlation with lymphatic metastasis(P＜0.01),and positive correlation with spiculation sign(P＜0.05);the size of nodules was significant negatively correlated with attenuation chacteristic of those nodules(P＜0.01);The inmplete lumen MVD in the surrounding zone were positively correlated with the deep lobulation and vacuolar sign and vessel convergence and lymphatic metastasis,respectively(P＜0.05).(5)The relationship among the MSCT perfusion parameters and the clinicopathological characters and 2D-TMAP and the heterogeneity of 3D-TMAP in NSCLC showed that;Degree of differentiation was significant negatively correlated with the surrounding area BF(P＜0.01),and negatively correlated with the total BF and the total BV and the total PEI,respectively(P＜0.05);The inmplete lumen MVD in the surrounding zone were negatively correlated with the surrounding area BF(P＜0.05),and also negatively correlated with the total BF and the total BV and the total PEI,respectively(P＜0.05);PCNA expression had significant negatively correlations with the surrounding area BF(P＜0.01),and also negatively correlations with the total BF and the total BV and the total PEI,respectively(P＜0.05);The CV was significant negatively correlated with the surrounding area BF(P＜0.01),and also negatively correlated with the total BF and the M/G(P＜0.05).(6)The influence on the exploration of CT perfusion mechanisms with the heterogeneity of 3D-TMAP:in the five sets of data of the MVD and the VEGF expression intensity,the two sets of those data showed the BF and the PEI and the M/G of malignant nodules was positively correlated with the MVD of that(P＜0.05),but the other three showed no correlation(P＞0.05).Conclusion:(1)Perfusion parameters reflects the density difference of vascular with the mature functional lumen,exact evaluates the differences of blood flow pattern in pulmonary space-occupying lesions,then to identify the lesions and the degree of lung cancer differentiation;(2)In the absence of central necrosis,the perfusion parameters gained from the conventional method are better at the overall evaluation of nodules than others.In order to exactly evaluate the degree of nodules differentiation,the preferred value is the surrounding area BF.(3)During study on the mechanism of MSCT pulmonary perfusion imaging,if we do not select the entirely consistent pathological specimens with the interest areas,it would get wrong conclusions.(4)The vacuolar sign,short burr,non-solid nodules,pleural retraction,bronchial sign and vascular gathered-sign are great significance to the diagnosis of malignant nodules.(5)The T-MAP of NSCLC regulates angiogenesis and proliferation by a mesh structure.The concepts in past years that to use a single factor to answer the complex question of biology in cancer research to be updated.(6)The biological behavior of NSCLC at least has two distinctly different stages.Put the different stages of the disease together for statistical analysis,it is unreasonable and unscientific.