Vascular immunohistochemical markers: contributions to hepatocellular nodule diagnosis in explanted livers

The process of hepatic carcinogenesis involves a progression including large regenerative nodules, to dysplastic nodules, and finally to hepatocellular carcinoma. Angiogenesis is fundamental to the development of malignant tumors. Changes in sinusoidal capillarization and isolated arteries occur early in hepatic carcinogenesis. However, sometimes differentiation of hepatocellular nodules can be difficult for the general pathologist. The aim of this study was to evaluate angiogenesis by immunohistochemistry using CD34 and HHF35 antibodies for differential diagnosis of large regenerative nodules versus dysplastic nodules versus hepatocellular carcinoma using explanted cirrhotic livers.

Seventy-nine nodules obtained from 29 explanted cirrhotic livers were classified according to the International Working Party as follows: 17 large regenerative, 23 low-grade dysplastic, 23 high-grade dysplastic, and 16 hepatocellular carcinomas. These nodules were submitted to immunohistochemistry with antibodies to CD34 and HHF35 to analyze sinusoidal capillarization and arterialization, respectively.

Semiquantitative analysis revealed that CD34 expression was >30% in dysplastic nodules and hepatocellular carcinoma; the staining in 93.8% of cases was diffuse, almost involving the entire sinusoidal lining in hepatocellular carcinoma. The number of isolated arteries was high in hepatocellular carcinoma (average, 4.369), which positively correlated with the other nodules (P < .005).

Quantification of sinusoidal capillarization and isolated arteries in hepatocellular nodules, as detected with CD34 and HHF35 antibodies, respectively provided an important tool to differentiate dysplastic nodules from hepatocellular carcinoma.