Molecular biological analysis of angiogenetic process of hepatocellular carcinoma, from the view point of standardization of diagnosis and treatment

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To elucidate the relationship between angiographic features and histological findings, an immunohistological study of alpha-smooth muscle actin was performed in 106 patients with small hepatocellular carcinoma. Arterial dominance or portal blood paucity were found in 73 patients (68.9%) on digital subtraction angiography, 88 (83.0%) on computerized tomographic arterial portography, and 87 (82.1%) on carbon dioxide-enhanced ultrasonography. Among 73 patients with hypervascularity on angiography, 57 (78.1%) had thick-walled, nuclei-rich, and slender-shaped vessels (Type II), 8 (11.0%) had thin-walled, nuclei-poor, and oval-shaped vessels. (Type I), and the remaining 8 had a mixed type of II and Type I. Conversely among 33 patients without hypervascularity, 5 (15.2%) had a Type II, 21 (63.6%) had a Type I, 5 had a mixed type, and 2 had no positive vessel. Tumor size, histological classification, and amount of non-triadal vessels were also associated with the angiographic appearance of the … More tumors. Among varied aspects of the cancer including tumor size, tumor multiplicity, microscopic portal invasion, histological classification, amount of alpha-smooth muscle actin-positive vessels, and shape of alpha-smooth muscle actin-positive vessels, multivariate logistic regression analysis demonstrated that the shape of alpha-smooth muscle actin positive vessels was solely associated with angiographic hypervascularity independently. Although the existence of non-triadal vessel characterized hepatocellular carcinoma, angiographic hypervascularity was closely associated with the Type II vessel. A morphological change of non-triadal vessel from Type I to Type II was considered to occur in an early stage of hepatocellular carcinoma.Eleven surgically resected specimens of well-differentiated hepatocellular carcinoma were analyzed for neovascular structure using monoclonal alpha-smooth muscle actin antibody. Each paraffin specimen was serially sliced with a thickness of 3 micrometers for immunohistochemistry. All of the eleven liver cancers had thin-walled, round-or oval-shaped non-triadal vessels in their well-differentiated parts. Immunohistochemistry of serial thin sections of HCC showed that these non-triadal vessels were connected to portal veins in portal triads in well-differentiated cancer in a total of nine patients (81.8%). This type of neovascular structure found in a well-differentiated cancer seemed to be a surviving portal vein among diminishing and disappearing arteries and bile ducts. All eleven tumors showed isovascular staining on ordinary digital subtraction angiography, and four of the tumors showed "negative enhancement" on intra-arterial carbon dioxide-enhanced ultrasonography or computerized tomographic hepatic arteriography, suggesting a relative arterial blood scarcity in the tumor nodules. Less