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. 1991 Mar;138(3):647–654.

Evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens.

W F Grigioni 1, S Garbisa 1, A D'Errico 1, P Baccarini 1, W G Stetler-Stevenson 1, L A Liotta 1, A M Mancini 1
PMCID: PMC1886291  PMID: 1848041

Abstract

Invasion and metastasis requires a series of interactions between malignant cells and the extracellular matrix (ECM). Antigen markers that relate to these interactions were evaluated for prognostic correlation in human hepatocellular carcinoma. Basement membrane type IV collagen (cIV), type IV collagenase (cIVase), laminin, and laminin receptors (LRs)--all ECM antigens previously proposed to be modulated in association with tumor aggressiveness--were immunohistochemically investigated in 30 cases of hepatocellular carcinomas (HCCs). The pattern of antigen expression was correlated with 1) 36 months' clinical follow-up and 2) the pathologic grade. As a means of estimating the proliferation fraction, an additional antigen, Ki67, was also studied in this series. There were major differences in the distribution of cIV and laminin, and in the quantity of cIVase-, LR-, and Ki67-positive cells associated with grade and prognosis. A smaller quantity of cIV and laminin and a higher number of cIVase-, LR-, and Ki67-positive cells were detected in the poorly differentiated compared with the well-differentiated HCCs. The tumors with lower immunoreactivity for cIV and laminin components accompanied by a higher number of cIVase-, LR-, and Ki67-positive cells fall into a group with the poorest overall survival (P less than 0.006). The panel of antigens is proposed as a useful prognostic tool for evaluating HCC tumor aggressiveness.

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Selected References

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  1. Barsky S. H., Siegal G. P., Jannotta F., Liotta L. A. Loss of basement membrane components by invasive tumors but not by their benign counterparts. Lab Invest. 1983 Aug;49(2):140–147. [PubMed] [Google Scholar]
  2. Bianchi F. B., Biagini G., Ballardini G., Cenacchi G., Faccani A., Pisi E., Laschi R., Liotta L., Garbisa S. Basement membrane production by hepatocytes in chronic liver disease. Hepatology. 1984 Nov-Dec;4(6):1167–1172. doi: 10.1002/hep.1840040612. [DOI] [PubMed] [Google Scholar]
  3. D'Errico A., Biagini G., Garbisa S., Milani M., Rizzoli R., Vasi V., Villanacci V., Grigioni W. F., Mancini A. M. Detection of extracellular matrix antigens (fibronectin, laminin, type IV in collagen) in paraffin embedded sections by avidin-biotin-peroxidase complex labelling. Basic Appl Histochem. 1986;30(3):325–332. [PubMed] [Google Scholar]
  4. Donato M. F., Colombo M., Matarazzo M., Paronetto F. Distribution of basement membrane components in human hepatocellular carcinoma. Cancer. 1989 Jan 15;63(2):272–279. doi: 10.1002/1097-0142(19890115)63:2<272::aid-cncr2820630212>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  5. EDMONDSON H. A., STEINER P. E. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954 May;7(3):462–503. doi: 10.1002/1097-0142(195405)7:3<462::aid-cncr2820070308>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  6. Gerdes J., Schwab U., Lemke H., Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983 Jan 15;31(1):13–20. doi: 10.1002/ijc.2910310104. [DOI] [PubMed] [Google Scholar]
  7. Gospodarowicz D., Greenburg G., Birdwell C. R. Determination of cellular shape by the extracellular matrix and its correlation with the control of cellular growth. Cancer Res. 1978 Nov;38(11 Pt 2):4155–4171. [PubMed] [Google Scholar]
  8. Grigioni W. F., Biagini G., Errico A. D., Milani M., Villanacci V., Garbisa S., Mattioli S., Gozzetti G., Mancini A. M. Behaviour of basement membrane antigens in gastric and colorectal cancer. Immunohistochemical study. Acta Pathol Jpn. 1986 Feb;36(2):173–184. doi: 10.1111/j.1440-1827.1986.tb01471.x. [DOI] [PubMed] [Google Scholar]
  9. Grigioni W. F., Biagini G., Garbisa S., D'Errico A., Milani M., Mastrorilli M., Vasi V., Villanacci V., Gozzetti G., Mancini A. M. Immunohistochemical study of basement membrane antigens in bronchioloalveolar carcinoma. Am J Pathol. 1987 Aug;128(2):217–224. [PMC free article] [PubMed] [Google Scholar]
  10. Grigioni W. F., D'Errico A., Bacci F., Gaudio M., Mazziotti A., Gozzetti G., Mancini A. M. Primary liver neoplasms: evaluation of proliferative index using MoAb Ki67. J Pathol. 1989 May;158(1):23–29. doi: 10.1002/path.1711580107. [DOI] [PubMed] [Google Scholar]
  11. Grigioni W. F., D'Errico A., Mancini A. M., Biagini G., Gozzetti G., Mazziotti A., Garbisa S. Hepatocellular carcinoma: expression of basement membrane glycoproteins. An immunohistochemical approach. J Pathol. 1987 Aug;152(4):325–332. doi: 10.1002/path.1711520411. [DOI] [PubMed] [Google Scholar]
  12. Guzelian P. S., Diegelmann R. F. Localization of collagen prolyl hydroxylase to the hepatocyte. Studies in primary monolayer cultures of parenchymal cells from adult rat liver. Exp Cell Res. 1979 Oct 15;123(2):269–279. doi: 10.1016/0014-4827(79)90468-3. [DOI] [PubMed] [Google Scholar]
  13. Liotta L. A., Rao C. N., Barsky S. H. Tumor invasion and the extracellular matrix. Lab Invest. 1983 Dec;49(6):636–649. [PubMed] [Google Scholar]
  14. Liotta L. A. Tumor invasion and metastases--role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res. 1986 Jan;46(1):1–7. [PubMed] [Google Scholar]
  15. Liotta L. A., Wicha M. S., Foidart J. M., Rennard S. I., Garbisa S., Kidwell W. R. Hormonal requirements for basement membrane collagen deposition by cultured rat mammary epithelium. Lab Invest. 1979 Dec;41(6):511–518. [PubMed] [Google Scholar]
  16. Martinez-Hernandez A. The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis. Lab Invest. 1985 Aug;53(2):166–186. [PubMed] [Google Scholar]
  17. Monteagudo C., Merino M. J., San-Juan J., Liotta L. A., Stetler-Stevenson W. G. Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol. 1990 Mar;136(3):585–592. [PMC free article] [PubMed] [Google Scholar]
  18. Okuda K., Peters R. L., Simson I. W. Gross anatomic features of hepatocellular carcinoma from three disparate geographic areas. Proposal of new classification. Cancer. 1984 Nov 15;54(10):2165–2173. doi: 10.1002/1097-0142(19841115)54:10<2165::aid-cncr2820541017>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  19. Scher W. The role of extracellular proteases in cell proliferation and differentiation. Lab Invest. 1987 Dec;57(6):607–633. [PubMed] [Google Scholar]
  20. Wewer U. M., Taraboletti G., Sobel M. E., Albrechtsen R., Liotta L. A. Role of laminin receptor in tumor cell migration. Cancer Res. 1987 Nov 1;47(21):5691–5698. [PubMed] [Google Scholar]
  21. Yamamoto M., Sumiyoshi H., Nakagami K., Tahara E. Distribution of collagen types I, III, and V in fibrotic and neoplastic human liver. Acta Pathol Jpn. 1984 Jan;34(1):77–86. doi: 10.1111/j.1440-1827.1984.tb02184.x. [DOI] [PubMed] [Google Scholar]

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