AbstractThe 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 (≥ 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. ©