Abstract
A case of cirrhotic liver harbouring three atypical macroregenerative nodules and an hepatocellular carcinoma was immunocytochemically investigated for the expression of VLA-β 1, VLA-α2 and VLA-α5 integrins and for different extracellular matrix (ECM) components (collagen I, collagen IV, laminin, fibronectin and tenascin). In addition, the proliferative activity within the nodules was evaluated, using the MIB 1 monoclonal antibody (MAb). The cirrhotic liver disclosed a continuous staining pattern of the ECM proteins investigated, as well as a “sinusoidal” immunostaining of VLA-β1, VLA-α2 and VLA-α5. The macroregenerative nodules showed a discontinued immunoreactivity for ECM proteins while maintaining a VLA-β1 sinusoidal immunostaining, coupled with intercellular immunostaining. VLA-α2 and VLA-α5 expression was lacking. The growth fraction was low in both the above pathological conditions. The hepatocellular carcinoma was devoid of any ECM immunostaining. VLA-β1 immunoreactivity exhibited a honeycomb pattern of staining, whereas VLA α subunits were absent. MIB1 expression was high, being present in 30% of neoplastic nuclei. A possible relationship between atypical macroregenerative nodules and hepatocellular carcinoma is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albrechtsen R, Wewer UM, Thorgeirsson SS (1988) De novo deposition of laminin-positive basement membrane in vitro by normal hepatocytes and during hepatocarcinogenesis. Hepatology 8: 538–546
Anthony PP (1979) Hepatic neoplasms. In: MacSween RNM, Anthony PP, Scheuer PJ (eds) Pathology of the liver. Churchill Livingstone, London, pp 387–414
Argraves WS, Pyetela R, Suzuki S, Millan JL, Pierschbacher MD, Ruoslahti E (1986) c-DNA sequences from the α subunit of the fibronectin receptor predict a transmembrane domain and a short cytoplasmic peptide. J Biol Chem 261: 12922–12924
Donato MF, Colombo M, Matarazzo M, Paronetto F (1989) Distribution of basement membrane components in human hepatocellular carcinoma. Cancer 63: 272–279
Edmonson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48900 necropsies. Cancer 7: 462–503
Ferrell L, Wright T, Lake J, Roberts J, Ascher N (1992) Incidence and diagnostic features of macroregenerative nodules vs. small hepatocellular carcinoma in cirrhotic livers. Hepatology 16: 1372–1381
Ferrell L, Crawford JM, Dhillon AP, Scheuer PJ, Nakanuma Y (1993) Proposal for standardized criteria for the diagnosis of benign, borderline and malignant hepatocellular lesions arising in chronic advanced liver disease. Am J Surg Pathol 17: 1113–1123
Furuya K, Nakamura M, Yamamoto Y, Togei K, Otsuka H (1988) Macroregenerative nodule of the liver, a clinicopathologic study of 345 autopsy cases of chronic liver disease. Cancer 61: 99–105
Garcia-Monzon C, Moreno-Otero R, Garcia-Buey L, Garcia-Sanchez A, Campanero MR, Sanchez-Madrid F (1992) Intrahepatic up-regulated expression of extracellular matrix protein receptors in chronic active hepatitis type B. Gastroenterology 102: 255–262
Gerdes J, Schlueter LLC, Duchrow M, Wohlenberg C, Gerlach C, Stahmer I, Kloth S, Brandt E, Flad HD (1991) Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 138: 867–873
Grigioni WF, Garbisa S, D'Errico A, Baccarini P, Stetler-Stevenson WG, Liotta LA, Mancini AM (1991) Evaluation of hepatocellular carcinoma aggressiveness by a panel of extracellular matrix antigens. Am J Pathol 138: 647–654
Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48: 549–554
Hynes RO (1992) Integrins: versatility, modulation, and si gnaling in cell adhesion. Cell 69: 11–25
Kondo F, Wada K, Nagato Y, Nakajima T, Kondo Y, Hirooka N, Ebara M et al. (1989) Biopsy diagnosis of well-differentiated hepatocellular carcinoma based on new morphologic criteria. Hepatology 9: 751–755
Martinez-Hernandez A, Amenta PS (1993a) The hepatic extracellular matrix. I. Components and distribution in normal liver. Virchows Arch [A] Pathol Anat 423: 1–11
Martinez-Hernandez A, Amenta PS (1993b) The hepatic extracellular matrix. II. Ontogenesis, regeneration and cirrhosis. Virchows Arch [A] Pathol Anat 423: 77–84
Martinez-Hernandez A, Delgado FM, Amenta PS (1991) The extracellular matrix in hepatic regeneration, localization of collagen types I, II, IV, laminin, and fibronectin. Lab Invest 64: 157–166
Mendler M, Priest A, Bourdon MA (1991) Tenascin is recognized by two different integrin receptors, aβ1-group integrin (αβ1) and the vitronectin receptor (αvβ3). 31st Congress Am Soc Cell Biol, J Ce Il Biol 115: 137a
Nakanuma Y, Terada T, Terasaki S, Ueda K, Nonomura A, Kawahara E, Matsui O (1990) ‘Atypical adenomatous hyperplasia’ in liver cirrhosis: low-grade hepatocellular carcinoma or borderline lesion? Histopathology 17: 27–35
Nakanuma Y, Terada T, Ueda K, Terasaki S, Matsui O (1993) Adenomatous hyperplasia of the liver as a precancerous lesion. Liver 13: 1–9
Patriarca C, Roncalli M, Gambacorta M, Cominotti M, Coggi G, Viale G (1993) Patterns of integrin common chain β1 and collagen IV immunoreactivity in hepatocellular carcinoma. Correlations with tumour growth rate, grade and size. J Pathol 170: 5–11
Plantefaber LC, Hynes RO (1989) Changes in integrin receptors on oncogenically transformed cells. Cell 56: 281–290
Ruoslahti E (1991) Integrins. J Clin Invest 87: 1–5
Ruoslahti E, Pierschbacher MD (1987) New perspectives in cell adhesion: RDG and integrins. Science 239: 491–497
Shi SR, Key ME, Kalra KL (1991) Ant igen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39: 741–748
Shi Z-R, Itzkowitz SI, Kim Y (1988) A comparison of three immunoperoxidase techniques for antigen detection in colorectal carcinoma tissues. J Histochem Cytochem 36: 317–322
Staatz WD, Rajpara SM, Wayner EA, Carter WG, Santoro SA (1989) The membrane glycoprotein Ia-IIa (VLA-2) comple x mediates the Mg++-dependent adhesion of platelets to collagen. J Cell Biol 108: 1917–1924
Terada T, Nakanuma J (1992) Cell proliferative activity in adenomatous hyperplasia of the liver and small hepatocellular carcinoma. An immunohistochemical study demonstrating proliferating cell nuclear antigen. Cancer 70: 591–598
Terada T, Terasaki S, Nakanuma Y (1993a) A clinicopathologic study of adenomatous hyperplasia of the liver in 209 consecutive cirrhotic livers examined by autopsy. Cancer 72: 1551–1556
Terada T, Ueda K, Nakanuma Y (1993b) Histopathological and morphometric analysis of atypical adenomatous hyperplasia of human cirrhotic livers. Virchows Arch [A] Pathol Anat 422: 381–388
Volpes R, Van Den Oord JJ, Desmet VJ (1991) Distribution of the Vla family of integrins in normal and pathological human liver tissue. Gastroenterology 101: 200–206
Volpes R, Van Den Oord JJ, Desmet VJ (1993) Integrins as differential cell lineage markers of primary liver tumors. Am J Pathol 142: 1483–1492
Yamada S, Ichida T, Matsuda Y, Miyazaki Y, Hatano T, Hata K, Asakura H, Hirota N, Geerts A, Wisse E (1992) Tenascin expression in human chronic liver disease and hepatocellular carcinoma. Liver 12: 10–16
Author information
Authors and Affiliations
Additional information
This paper was partly presented at the 35th Symposium of the Society for Histochemistry, Gargellen, Austria, Sept. 29–Oct. 3, 1993
Rights and permissions
About this article
Cite this article
Patriarca, C., Roncalli, M., Viale, G. et al. Extracellular matrix proteins, integrin receptors (VLA-β1, VLA-α2 and VLA-α5) and growth fraction in atypical macroregenerative nodules of the liver: an immunocytochemical case study. Histochemistry 102, 29–36 (1994). https://doi.org/10.1007/BF00271046
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00271046