HCRP1, ID4 and Glypican-3: an optimal panel of biomarkers for diagnosis of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with high morbidity and mortality. The aim of this study was to assess the diagnostic role of HCC related protein 1 (HCRP1) and inhibitor of DNA Binding 4 (ID4) as novel reliable markers for HCC diagnosis.

Methods: Immunohistochemistry for HCRP1, ID4 and Glypican-3 (GPC-3) was performed in 98 cases of HCCs, 15 large regenerative nodules arising in cirrhotic livers, 12 hepatocellular adenomas (HCA), 10 focal nodular hyperplasias (FNH), and 20 specimens of normal liver tissues (NL).

Results: HCRP1 immunoactivity was decreased in 64 of 98 (65.3%) HCC cases but present in almost all of the benign liver nodules (56/57, 98.2%, < 0.001). 68 of 98 (69.4%) and 70 of 98 (71.4%) HCC cases were positive for ID4 and GPC-3, respectively, which were much higher than in benign lesions. Even though HCRP1 is highly specific (98.25%) in differentiating well differentiated HCC (WDHCC) from benign liver nodules, it has only a limited value because of its low sensitivity (37.5%), neither for the ID4, GPC-3 alone or combination ( > 0.05). The expression of HCRP1 alone could efficiently distinguish WDHCC from moderate-poorly differentiated HCC (M-PHCC), and the combination of using either two or three markers could notably increase the diagnosis accuracy ( < 0.05).

Conclusion: HCRP1 and ID4 represent potentially novel valuable biomarkers for distinguishing HCC from benign liver nodules, and it is recommended to use the combination of HCRP1, ID4 and GPC-3 as a panel in HCC differentiation estimation.