Biological markers in hepatocellular carcinoma: potential clinical implications

The assessment of biological markers as potential indicators of disease aggressiveness is still an open problem in hepatocellular carcinoma. Cell proliferation and extracellular matrix (ECM)-associated antigens and tumor-cell products can be associated with clinical aggressiveness in this tumor type, as has already been demonstrated for others. Cell proliferation, expressed as the in vitro [3H]thymidine labeling index, and ECM-associated antigens, such as type IV collagenase and laminin receptors, were assessed on the same paraffin-embedded samples. A strong association (P = 0.0001) was observed between the expression of collagenase and laminin receptors, with a correlation coefficient (rs) of 0.68. No relationship was found between cell proliferation and ECM-associated antigens. Moreover, the biological markers were generally independent of clinicopathologic features, except for a higher number of collagenase- and laminin receptor-positive cells in large (> or = 5 cm) compared with small (< 5 cm) tumors. In the present series of hepatocellular carcinoma patients, the 3-year clinical outcome was significantly affected by cell proliferation and ECM-associated antigens.