Expression of c-kit protooncogen in hepatitis B virus-induced chronic hepatitis, cirrhosis and hepatocellular carcinoma: has it a diagnostic role?

AIM

There are more than 350 million people worldwide chronically infected with hepatitis B virus (HBV), who are at high risk for the development of hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Because of the conflicting results about c-kit expression in HCC and the key role played by c-kit in gastrointestinal stromal tumours (GIST) and other solid tumours, the aim of this study was to determine c-kit expression in the course of hepatitis B infection.

MATERIALS AND METHODS

Paraffin-embedded tissues in Cukurova University Faculty of Medicine Department of Pathology between January 2002 and February 2006 were searched restrospectively to investigate this issue. We performed immunohistochemistry on biopsies of 125 patients with HBV infection, grouped as: mild, moderate and severe hepatitis, cirrhosis and HCC, 25 patients in each of them, using anti c-kit monoclonal antibody. The severity of parenchymal inflammation and of interface hepatitis was semiquantitatively graded on a haematoxylin and eosin stained paraffin sections. Additionally, 50 more HCC, formed on HBV basis, were studied to determine the prevalence of c-kit overexpression.

RESULTS

In cirrhotic liver, lower intensity of staining and rarely c-kit positivity were present. The greatest number of the c-kit positivity and higher intensity of staining was found in the livers of patients with severe hepatitis and HCC. In chronic hepatitis B infection, the staining intensity was parallel with the grade and stage of the disease. In the areas where fibrosis was seen, c-kit positivity was rare or absent. In the HCC specimens, c-kit positivity appeared both inside and around the cancerous nodes. C-kit expression was observed in 62 of 75 HCC tissue specimens (82%) (p < 0.001).

CONCLUSIONS

C-kit positivity was observed in the mitotic, proliferating and also dysplastic hepatic cells. These results suggest that c-kit expression may be used as an early diagnostic indicator for HBV induced HCC.