CD44 IS EXPRESSED IN HEPATOCELLULAR CARCINOMAS SHOWING VASCULAR INVASION

CD44 and its variant isoforms are a group of transmembrane glycoproteins which play important roles in immune recognition, in lymphocyte trafficking, and in cell–cell and cell–matrix interactions. Although CD44 is expressed by some normal human epithelial and mesenchymal cells, upregulation of CD44 expression has been related to the metastatic potential of some malignant tumours. In this study of 27 hepatocellular carcinomas (HCCs), an indirect immunohistochemical method was used to investigate the distribution of CD44 in normal liver and to determine whether 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, and eight were grade IV. Liver cell dysplasia was present in adjacent liver parenchyma in three cases and vascular invasion was observed in ten HCCs. Vascular invasion was found to be more frequent in high grade HCCs and a significant correlation was observed between tumour proliferation indices and vascular invasion. CD44s was not expressed by epithelial 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. There was a significant correlation between CD44 expression and the presence of vascular invasion, but not between CD44 expression and tumour grade or tumour proliferation indices. It is concluded that upregulation of cell surface CD44 expression on malignant hepatocytes is related to their tendency to vascular invasion and may have implications relating to metastasis and prognosis in patients with HCCs.

[1]  S. Fox,et al.  Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms. , 1994, Cancer research.

[2]  C. Mackay,et al.  Expression and modulation of CD44 variant isoforms in humans , 1994, The Journal of cell biology.

[3]  F M van den Berg,et al.  Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. , 1993, Cancer research.

[4]  G. Viale,et al.  Patterns of integrin common chain β1 and collagen IV immunoreactivity in hepatocellular carcinoma. Correlations with tumour growth rate, grade and size , 1993, The Journal of pathology.

[5]  J. Jessup,et al.  CD44 participates in the adhesion of human colorectal carcinoma cells to laminin and type IV collagen. , 1993, Surgical oncology.

[6]  A. Nakao,et al.  Expression of intercellular adhesion molecule‐1 in hepatocellular carcinoma , 1993, Journal of surgical oncology.

[7]  P. Herrlich,et al.  Activated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis-associated variant of CD44 , 1993, The Journal of experimental medicine.

[8]  P. Hall,et al.  Detection of the Ki‐67 antigen in fixed and wax‐embedded sections with the monoclonal antibody MIB1 , 1993, Histopathology.

[9]  L. Ellis,et al.  Expression of CD44R1 adhesion molecule in colon carcinomas and metastases , 1993, The Lancet.

[10]  P. Herrlich,et al.  The two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior. , 1993, Cancer research.

[11]  P. Herrlich,et al.  Prevention of tumor metastasis formation by anti-variant CD44 , 1993, The Journal of experimental medicine.

[12]  P. Herrlich,et al.  A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps , 1993, The Journal of cell biology.

[13]  D. Tarin,et al.  Significance of CD44 gene products for cancer diagnosis and disease evaluation , 1992, The Lancet.

[14]  C. Underhill,et al.  CD44: the hyaluronan receptor. , 1992, Journal of cell science.

[15]  H. Liao,et al.  The transmembrane hyaluronate receptor (CD44): multiple functions, multiple forms. , 1991, Cancer cells.

[16]  Martin Hofmann,et al.  A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells , 1991, Cell.

[17]  L. Liotta,et al.  Evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens. , 1991, The American journal of pathology.

[18]  P. Herrlich,et al.  Retardation of metastatic tumor growth after immunization with metastasis‐specific monoclonal antibodies , 1990, International journal of cancer.

[19]  S. Albelda,et al.  Integrins and other cell adhesion molecules , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  K. Miyake,et al.  Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition , 1990, The Journal of experimental medicine.

[21]  P. Herrlich,et al.  CD44 splice variants; expression on lymphocytes and in neoplasia. , 1993, Research in immunology.

[22]  D. Tarin,et al.  Deranged activity of the CD44 gene and other loci as biomarkers for progression to metastatic malignancy , 1993, Journal of cellular biochemistry. Supplement.

[23]  S. Albelda,et al.  Role of integrins and other cell adhesion molecules in tumor progression and metastasis. , 1993, Laboratory investigation; a journal of technical methods and pathology.