CD44 IS EXPRESSED IN HEPATOCELLULAR CARCINOMAS SHOWING VASCULAR INVASION

CD44 and its variant isoforms are a group of transmembrane glycoprotei ns which play important roles in immune recognitions, in lymphocyte tr afficking, and in cell-cell and cell-matrix interactions. Although CD4 4 is expressed by some normal human epithelial and mesenchymal cells, upregulation of CD44 expression has been related to the metastatic pot ential of some malignant tumours. In this study of 27 hepatocellular c arcinomas (HCCs), an indirect immunohistochemical method was used to i nvestigate the distribution of CD44 in normal liver and to determine w hether expression of the standard form of CD44 (CD44s), or two of its variant isoforms (CD44-v3 and CD44-v6), correlated with tumour grade, proliferation indices, or histological evidence of vascular invasion. Fifteen of the tumours were Edmondson grade II, four were grade III, a nd eight were grade IV. Liver cell dysplasia was present in adjacent l iver parenchyma in three cases and vascular invasion was observed in t en HCCs. Vascular invasion was found to be more frequent in high grade HCCs and a significant correlation was observed between tumour prolif eration indices and vascular invasion. CD44s was not expressed by epit helial cells of normal liver but was expressed by tumour cells in six HCCs; vascular invasion was present in five of these HCCs. Three CD44s -positive cases also expressed CD44-v3 and two of these also expressed CD44-v6. CD44 was not expressed in areas of hepatocyte dysplasia. The re was a significant correlation between CD44 expression and the prese nce of vascular invasion, but not between CD44 expression and tumour g rade or tumour proliferation indices. It is concluded that upregulatio n of cell surface CD44 expression on malignant hepatocytes is related to their tendency to vascular invasion and may have implications relat ing to metastasis and prognosis in patients with HCCs.