Angiogenesis in hepatocellular carcinoma as evaluated by alpha smooth muscle actin immunohistochemistry.
OBJECTIVE
Angiogenesis has been known to be associated with tumor development. In this study, neovascularization in small hepatocellular carcinoma was investigated by evaluation of intratumoral arteriole counts, using alpha smooth muscle actin antibody immunohistochemistry.


METHODS
Surgical specimens from 38 patients with small hepatocellular carcinoma were immunostained for alpha smooth muscle actin and proliferating cell nuclear antigen. The correlation between intratumoral arteriole density and clinicopathological factors including angiographic findings, proliferative activity, and patient prognosis were analyzed.


RESULTS
Significant difference in intratumoral arteriole density were observed between well-differentiated hepatocellular carcinoma and poorly differentiated hepatocellular carcinoma (P = 0.004) or moderately differentiated hepatocellular carcinoma and poorly differentiated hepatocellular carcinoma (P = 0.011). The mean intratumoral arteriole count in the tumors showing angiographic hypervascularity was significantly higher than that in the tumors without angiographic hypervascularity (P = 0.011). A significant and positive correlation was found between proliferating cell nuclear antigen labeling index and intratumoral arteriole density (r = 0.5232, P = 0.001). A high intratumoral arteriole density in tumor was significantly correlated with shorter patients survival (P = 0.018). Cox's multivariate regression analysis showed that the intratumoral arteriole density was independent prognostic factors (P = 0.0306).


CONCLUSIONS
Intratumoral arteriole density was found to be significantly associated with histological grade, proliferative activity, and patient survival. It also reflected the angiographic findings. Alpha smooth muscle actin antibody immunohistochemistry would provide a simple and biologically significant method which is usable to screen neovascularization and arterial blood supply in hepatocellular carcinoma, and may have predicting utility for patients outcome. This technique is applicable to routine paraffin sections, and may be useful as an adjunct to surgical pathology of hepatocellular carcinoma.
Morinaga
S
S
First Department of Surgery, Yokohama City University, School of Medicine 3-9 Fukuura, Kanazawaku, Yokohama 236-0004, Japan.
Imada
T
T
Shimizu
A
A
Akaike
M
M
Sugimasa
Y
Y
Takemiya
S
S
Takanashi
Y
Y
D000199:Actins / Q000032:analysis*; D000328:Adult; D000368:Aged; D000792:Angiography; D001160:Arterioles / Q000737:chemistry / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D015996:Survival Rate
D000199:Actins; D018809:Proliferating Cell Nuclear Antigen