非小细胞肺癌组织中EphB4和ephrinB2的表达与CT肺灌注成像的关系

Relationship between multi-slice spiral CT pulmonary perfusion imaging and the expression of EphB4 and ephrinB2 in non-small cell lung cancer

目的探讨非小细胞肺癌（NSCLC）组织中EphB4和ephrinB2的表达及其与CT肺灌注成像的关系。方法对31例NSCLC患者的肺内单发结节行CT灌注成像，获得血流量（BF）、血容量（BV）和最高增强值（PEI）数据。采用免疫组化SP法检测EphB4和ephrinB2在肿瘤细胞与问质血管中的表达。运用Spearman相关分析与趋势检验探讨EphB4和ephrinB2蛋白表达与NSCLC临床病理特征、灌注参数的关系。结果31例NSCLC组织中，22例（71．0％）Ephl34表达阳性，26例（83．9％）ephrinB2表遗阳性，明显高于内对照（分别为24．0％和20．3％，P〈0．01）。EphB4和ephrinB2的表达在肿瘤细胞中有一致性，在肿瘤间质血管中有差异性。EphB4和ephrinB2蛋白表达强度与淋巴结转移均呈低度正相关（r=0．370，P=0．045；r=0．362，P=0．047）。31例NSCLC患者BF为（42．3±10．2）ml·100mg^-1·min^-1，BV为（9．0±3．9）ml／100g，PEI为（21．6±8．4）HU。相关分析显示，在NSCLC肿瘤细胞中，EphB4的表达强度分别与BF和BV呈负相关（r=-0．452，P=0．011；r=-0．408，P=0．023），与PEI无关。ephrinB2的表达强度分别与BF和BV呈正相关（r=0．516，P=0．003；r=0．448，P=0．013），与PEI无关。EphB4表达强阳性组和阳性组的BF与BV值均显著低于EphB4表达阴性组（均P〈0．01）。ephrinB2表达强阳性组的BF值显著高于ephrinB2表达阳性组和阴性组（均P〈0．01），ephrinB2表达强阳性组的BV值显著高于ephrinB2表达阴性组（P〈0．01）。结论灌注成像反映功能性管腔化血管的密度差异，这种差异同时取决于管腔化血管的数量与质量。

Objective To investigate the role of the expression of ephrinB2 and EphB4 in non-small cell lung cancer （NSCLC） , and their relationship with multi-slice spiral CT pulmonary perfusion imaging. Methods Thirty-one nodules with pathologically proven NSCLC underwent CT perfusion scan. The perfusion parameters including blood flow （BF）, blood volume （BV）, peak enhancement image （PEI）were collected. The expression of ephrinB2 and EphB4 in tumor cells and interstitial vasculature were detected by immunohistochemistry. Correlation analysis and trend test were used to assess the relationship between ephrinB2/EphB4 expression and clinicopathological features, and between ephrinB2/EphB4 expression and perfusion parameters. Results Positive expression of ephrinB2 and EphB4 in the NSCLC group was 83.9% and 71.0%, respectively, significantly higher than that in the internal control group （P 〈 0.01 ）. The expression of ephrinB2 and EphB4 was consistently in tumor parenchyma but differently in tumor vessels. The expressions of ephrinB2 and EphB4 were positively correlated with lymphatic metastasis （ P 〈 0.05 ）. The expression of EphB4 was negatively correlated with blood flow （BF） and blood volume （BV）, respectively （P 〈 0.05 ）. There was a significant positive correlation between ephrinB2 expression and BF （ r = 0.516,P = 0.003 ） , and a positive correlation between ephrinB2 expression and BV （ r = 0. 448, P = 0. 013 ）. The expressions of ephrinB2 and EphB4 were not correlated with PEI （P 〉 0.05 ）. The values of BF and BV in the high and moderate EphB4 expression groups were significantly decreased compared with that in the negative group （ P 〈 0.01 ）. The value of BF in the high ephrinB2 expression group was significantly increased compared with that in the moderately positive group and negative group （ P 〈 0.01 ）. The value of BV in the high ephrinB2 expression group was significantly increased compared with that in the negative group （ P 〈 0. 01 ）. Conclusion The CT pulmonary perfusion imaging reflects the density difference of blood vessels with functional lumen, and such difference also depends on the quantity and quality of vaseulature with functional lumen.