Role of angiogenesis in hepatitis and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is usually a hypervascular tumor. Factor VIII-related antigens, including von Willebrand factor, are known to be expressed in HCC, which cause capillarization of the sinusoids of HCC. Capillarization of hepatic sinusoids may play a role in hepatocarcinogenesis and its metastasis. The aim of this study is to clarify the expression of Factor VIII in patients with hepatitis B or C (n = 18) and HCC (n = 16).

All specimens were sufficient for immunohistochemical study of the neo-angiogenesis with regard to clinical results. Microvessel count per square millimeter (MVC) and hot spot of microvessel per square millimeter (HSV) were measured from the histochemical study.

In the patients with hepatitis group, the positive staining on the vessels of the portal triad was 11.1% (2/18) but in the non-neoplastic tissue of HCC patients the positive rate was 68.7% (11/16) showing a significant difference from the hepatitis group. The amount of vasculatures was easily found in the surrounding capsule of resected HCC. The MVC of the capsule was 10.17 +/- 2.78 and 13.66 +/- 5.42 for the HCC with non-direct invasion and direct invasion during operation, respectively. The HSV of capsules were 7.51 +/- 2.09 and 9.14 +/- 4.02 for the non-invasion and invasion, respectively. Therefore, in our study, it is clear that the high MVC or HSV scores were found in patients of direct invasion. However, there was no relation between hepatitis B or hepatitis C to the tumor invasiveness. The median survival times were 21.5 months for the non-invasive group and 14.5 months for the invasive group (p < 0.05). The positive rate of Factor VIII in the vessels of the portal triad were 60% and 83.3% for the non-invasive and invasive groups, respectively. However, the lower values of MVC and HSV showed a trend toward a longer recurrence time.

It is pertinent to prove that the high score of neo-angiogenesis has a high risk of recurrence. In addition, it is wise to pay more attention to the interval of the follow-up study to detect the recurrent lesion earlier, where possible, in the patient with a high score of microvascularity.