A monoclonal mouse antibody, Be-F4, was generated by means of immunization with a synthetic oligopeptide. In Western blots, this antibody recognizes an antigen with an apparent molecular mass of 62 kDa, termed p62. Immunohistochemical analysis of p62 in hepatocellular carcinoma (HCC) specimens (n=33) and in corresponding non-cancerous liver tissue was performed using monoclonal antibody Be-F4. All non-neoplastic hepatic cells showed, without exception, a moderate or strong staining intensity of the 62-kDa antigen, recognized by Be-F4. In contrast to the non-neoplastic hepatocytes, the cellular p62 content was unambiguously reduced in all malignant cells. The extent of decrease of p62 corresponded to the grade of histological differentiation of HCC cells (P<0.001). Using a semiquantitative scoring system, the median of p62 expression, which was 2.1 for normal hepatocytes, was significantly reduced to 1.2 for G1, 1.0 for G2, and 0.2 for G3 HCCs. These data suggest that neoplastic transformation is associated with a reduced p62 content.