肝细胞癌MSCT灌注成像及其与survivin表达、MVD及分化程度的相关性

MSCT perfusion imaging and its correlation with perfusion parameters,survivin expression,MVD,and pathologic grade in hepatocellular carcinomas

目的:(1)应用多层螺旋CT(MSCT)行肝脏CT灌注成像(CTPI)获得肝细胞癌(HCC)、癌旁肝组织、正常肝组织的血流灌注参数,探讨其特征及临床意义;(2)探讨HCC的灌注参数与survivin表达、微血管密度及病理分级之间的相关性。方法:HCC31例(高分化5例,中分化17例,低分化9例)、正常肝10例。采用Philips Brilliance16层螺旋CT机,依次行常规全肝平扫、灌注扫描及常规全肝增强扫描。于灌注扫描图像生成各兴趣区(ROI)的时间-密度曲线(TDC),并获得其灌注参数。采用免疫组织化学SABC法检测HCC组织、相应癌旁组织及正常肝组织中survivin表达和微血管密度(MVD)。将灌注成像参数值与survivin表达程度、MVD及病理分级作相关性分析。结果:(1)HCC肝动脉灌注量(HAP)、门静脉灌注量(HPP)、肝总灌注量(TLP)及肝动脉灌注指数(HAI)均值分别为27.50mL/(min.100mL),19.37mL/(min.100mL),46.87mL/(min.100mL)及60.38%;癌旁肝各均值分别为14.92mL/(min.100mL),55.70mL/(min.100mL),69.63mL/(min.100mL)及21.51%;正常肝组织各均值分别为12.22mL/(min.100mL),74.56mL/(min.100mL),86.78mL/(min.100mL)及14.00%。HCC的HAP和HAI值均较癌旁肝及正常肝组织明显增高(P<0.01),而HPP和TLP值均较正常肝组织明显减低(P<0.01);癌旁肝HAP值增加、HPP值减少,与正常肝组织有统计学差异(P<0.05);HCC与癌旁肝之间,除TLP值外,HAP,HPP和HAI值均有非常显著性差异(P<0.01)。(2)31例HCC中,23例survivin表达阳性(阳性率74.1%);HCC组织中Survivin的表达水平高于相应的癌旁组织和正常肝组织(P<0.01);survivin在HCC组织中的表达与MVD值呈正相关关系。(3)HCC组织中HAP值与survivin表达呈正相关(r=0.932,P<0.01)。(4)HAP和HAI值与HCC病理学分级相关,高、中、低分化肝癌的HAP、HAI值逐级递增,且有显著性差异(P<0.05)。结论:CTPI可定量地反映HCC血供的异常状况,有助于病灶的检测及鉴别诊断;HCC血流灌注参数值与survivin表达、MVD及病理分级均具有一定程度的相关性,说明CTPI可望用于在活体前瞻性地对HCC血管生成及相应的生物学行为进行无创、实时、动态的评价。

Objective （1）To obtain the perfusion parameters of hepatocellular carcinomas （HCCs） , peritumour livers and normal livers by multi-slice CT（MSCT） and to investigate their characteristics and clinical signifieances ; （ 2 ） To investigate the correlation among perfusion parameters, survivin expression, microvessel density （ MVD ） and pathologic grade of HCCs. Methods A total of 31 patients with HCC （5 well-differentiated HCCs, 17 moderately differentiated HCCs, and 9 poorly differentiated HCCs ） and 10 normal liver were studied. All underwent CT plain scan, perfusion scan, and conventional enhancement scan of the whole liver using 16-slice spiral CT （ Philips Brilliance （ ROI ） tissues 16 ）. Perfusion parameters were obtained by time-dens through the perfusion scans. Tissue sections of HCCs ity and of the 31 patients were detected by immunohistochemistry （ curves （ TDC ） of region of interest their corresponding peritumour liver SABC methods ） for protein expression of survivin and MVD, and 10 normal liver tissue sections were as used as negative controls. The correlation among the perfusion parameters, survivin expression, MVD and pathology grade were analysed. Results （ 1 ） The mean values of HAP, HPP, TLP, and HAI of HCCs were 27.50 mL/ （min · 100 mL）, 19.37 mL/（min · 100 mL）, 46.87 mL/（min · 100 mL）, and 60.38%, respectively. The mean values of those of the peritumour livers were 14.93 mL/（ min · 100 mL）,55.70 mL/（min · 100 mL）, 69.63 mL/（min · 100 mL）, and 21.51%, respectively. The mean value of those of the normal livers were 12.22 mL/（ min · 100mL） , 74.56 mL/（ min ·100 mL） , 86.78 mL/（min · 100 mL） , and 14.00% , respectively. The values of HAP and HAI of HCCs were significantly higher than those of the peritumor livers and the normal livers （P 〈0.01 , and the HPP and TLP of HCCs were significant lower than those of the normal livers （ P 〈 0.01 . The increase of HAP and decrease of HPP of peritumor livers were both significant compared with that of the normal livers （ P 〈 0.05 ）. The HAP, HPP, and HAI of HCCs were significantly different from those of peritumor livers （ P 〈 0.01 ） except TLP. （ 2 ） Survivin expression in HCCs was detected in 23/31 （74. 1% ）, which was significantly higher than that in corresponding noncancerous adjacent liver tissues and normal liver tissues （ P 〈 0. 01 ）. Survivin expression was positively correlated with MVD in HCCs. （3） HAP with survivin expression （ r = 0. 932, P 〈 0.01 ） values were significantly and positively correlated in HCCs. （4）The values of HAP and HAI were correlated with the pathologic grade in HCCs, and those values were increased gradually （ P 〈 0.05 ） among well differentiated HCCs, moderately differentiated, and poorly differentiated HCCs. Conclusion CTPI can quantitatively reflect abnormal blood supply of HCCs, which will be helpful for the detection and differentiation of lesions. CT perfusion parameters well correlate with survivin expression, MVD, and the pathologic grade in HCCs, which illustrate that CTPI could hopefully be used to evaluate the angiogenesis and biological behaviors of HCCs prospectively, noninvasively, and dynamically.