| Background and purpose: Hepatocellular carcinoma(HCC)is the most common malignancy of the liver. The use of spiral CT (SCT) has proved to be an effective method in early diagnosis treatment as well as predicting prognosis of HCC. Angiogenesis plays an important role to the growth and metastasis of the tumor. The microvessel density (MVD) is now widely used to evaluate the tumor giogenesis, and has been proved to correlate with the tumor infiltration and prognosis. Tumor is controlled by a number of angiogenic angiogenesis factors, among which vascular endothelial growth factor(VEGF) plays an important role in neovascularization, and has been proved to be related to aggressiveness and prognosis of many solid tumors. All imaging features are based on its pathological nature and determined by biological beheviors, so that a comparison between SCT features and its biologic behaviors may devote to the relationship between modern medical imaging and molecular biology. The purpose of this study was to evaluate the correlation between SCT features and carcinoma, investigate the ability of SCT assessing tumor neovascularization, understand deeply the significance of CT features of HCC and obtain more information for its diagnosis, selection of treatment decision and prognosis by SCT.Materials and methods: The MVD and expression of VEGF were examined by means of SP immunohistochemical technique in 45 cases of HCC proved by pathology. All patients were examined by normal and contrast-enhanced CT scanning, and had never been treated with non-operative management before operation, such as radiotherapy, chemotherapy and so on. Spiral CT examinations were performed with a Siemens Somatom Esprit helical scanner. After unenhanced spiral CT scans were performed, contrast medium Iohexol was injected intravenously with a power injector at a rates of 3.0-3.5ml/s.The volume of contrast medium Iohexol was 100ml.Two-phase enhanced spiral CT scans were obtained at 30-35s and 60-70s respectively after the beginning of injection. The scan parameters were 130KV 250- 300mA, collimation 5-10mm,pitch=1. Microvessel counting and calculation of VEGF expression percentage were observed at 400x magnification under the same standard respectively. The correlation of tumor grade with MVD and expression of VEGF was analyzed. The CT manifestations of pre-operation, including diameter of tumors, capsulae patterns, intrarumoral necrosis, metastasis and the enhancement patterns, were analyzed their relation to MVD and expression of VEGF. Statistical analysis was executed by SPSS 10.0 software .The enumeration data of the groups were compared using t-test and analysis and variance, the binaty data were compared using x~2 -test and Fisher's exact test, significant levelα=0.05.Results: (1) In 45 patients, VEGF expression was detected in 32 tumors, the VEGF positive were 71.1%(32/45). The microvessel densities ranged from 12.1 to 87.5 with a mean of 18.1-87.5(standard deviation, 16.2). The microvessel densities were 57.3±25.6 in VEGF positive tumors and 38.7±14.9 in VEGF negative tumors, and the difference was statistically significant(P<0.01). (2) The relation of pathologic grade, MVD and VEGF: The MVD in HCC of grade I, II, III and IV were 22.9±12.6, 36.7±16.2, 51.1±17.3 and 67.8±21.4, VEGF positive rates in HCC of grade I, II ,III and IV were 28.6%(2/7), 53.3%(8/15), 90.9%(10/11) and 100.0%(12/12). The pathologic grading of HCC was positively correlated with its MVD and expression of VEGF, in grade I and grade III～IV, II and grade IV (P＜0.05). There were no statistical correlation between I and II, II and IIIor between III and IV(P >0.05). (3) The correlation of CT features and MVD and expression of VEGF:①The MVD and VEGF positive rates in groups of HCC having blurred margin on SCT scans were 50.3±16.2, 90.0%(19/21), and in those tumors having clear margin were 38.7±17.6, 54.1%( 13/24), there was significant correlation (P<0.05 );②The MVD and VEGF positive rates were 65.3±17.6, 77.8%(7/9) in tumors having central necrosis and 38.2±13.0, 69.4%(25/36) in tumors without central necrosis, and the difference was statistically significant(P＜0.05);③The MVD and VEGF positive rates were 73.9±20.4, 100.0%(18/18) in tumors having high infiltration severity and 40.6±17.1, 51.8%(14/27) in tumoes without infiltration, and the difference was statistically significant(P<0.05);④The MVD and VEGF positive rates were 54.6±18.4, 75.0%(15/20) in rumors with diameter larger than 5.0cm and 46.1±16.5, 68.0%(17/25) in those with diameter less than 5.0cm, and there was no statistically significant correlation (P>0.05);⑤There were three blood supply types of HCC on spiral CT, The MVD and VEGF positive rates were 70.6±22.9, 85.1%(23/27) in tumors of arterial blood, 65.7±21.6,63.6%(7/11) in those of double blood supplying and 25.1±13.5,28.6%(2/7) in those of poor blood supplying, There was statistic difference of VEGF positive between arterial blood, or arterial combining with double blood supplying and poorly blood supply HCC respectively(P<0.05). In HCC with arterial and double blood supply, MVD expression level was higher than that with poor blood supplies (P <0.01).Conclusion (1) There was a close positive correlation between MVD and expression of VEGF, it is indicated that VEGF protein play an important role in neovascularization of HCC. (2) The pathologic grading of HCC was positively correlated with its MVD and expression of VEGF, it is demonstrated that they evaluate pathologic grading of HCC at a level. (3) The results showed that the features of HCC, including border, intratumoral necrosis, metastasis and the enhancement patterns, were significantly related to MVD and expression of VEGF, it is indicated that they play an important role in growth, aggressiveness and blood supply types of HCC. (4) To analyze the relationship between CT features and tumor neovascularization of HCC, the CT characteristic can be further realized. And the more information was obtained for its diagnosis selection of management and prognosis. Therefore, two-phase enhanced SCT scans may be a noninvasive method to predict aggressiveness and prognosis of HCC at molecular biological level. |
