Skip to main content
SpringerLink
Log in

Immunohistochemical demonstration of human carbonic anhydrase isoenzyme II in brain tumours

  • Papers
  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Summary

Carbonic anhydrase (CA) is a functionally important enzyme in the central nervous system (CNS), where it is involved in the control of the acid-base balance and regulates the production of cerebrospinal fluid (CSF). Isoenzyme II (CA II) is the most widely distributed CA in the CNS, being present in at least myelin, oligodendrocytes, astrocytes and the choroid plexus. This study was undertaken to examine the presence of CA II in different brain tumours from 31 patients. Specific antibodies recognizing CA II were used in immunoperoxidase staining of tumour specimens. Anti-CA I and VI sera and normal rabbit serum were used as controls. CA II-positive staining was observed in all the astrocytic tumours (n = 9), oligodendrogliomas (n = 3) and medulloblastomas (n = 3). The most malignant tumours exhibited the strongest staining. In addition, four acoustic neurinomas, one plexiform neurofibroma, one choroid plexus papilloma, one ependymoblastoma and one subependymoma expressed the enzyme. Meningiomas (n = 4) and neuronal tumours (N = 4), including one dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos), were negative. Anti-CA I, VI and normal rabbit sera showed no specific staining in tumour cells. The presence of CA II in the astrocytomas was confirmed by Western blotting, which revealed a distinct 29 kDa polypeptide band corresponding the CA II. Anti-CA I serum showed similarly a single 29 kDa band, recognizing the enzyme which is abundantly present in the erythrocytes. The present results demonstrate that despite the malignant transformation of the cells, the expression of CA II is sustained in astrocytic tumours, oligodendrogliomas, ependymal and choroid plexus tumours and tumours of nerve sheath cell origin. Our results suggest that some tumours contain abundant CA II, which might leak into the CSF.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Cammer,W. (1977) Carbonic anhydrase.Comp. Biochem. Physiol. 57B, 1–7.

    Google Scholar 

  • Cammer,W. (1991) Immunostaining of carbamoylphosphate synthase II and fatty acid synthase in glial cells in rat, mouse, and hamster brains suggests roles for carbonic anhydrase in biosynthetic processes.Neurosci. Lett. 129, 247–50.

    Article  CAS  PubMed  Google Scholar 

  • Cammer,W. &Tansey,F. A. (1988) The astrocyte as a locus of carbonic anhydrase in the brains of normal and dysmyelinating mutant mice,J. Comp. Neurol. 275, 65–75.

    Article  CAS  PubMed  Google Scholar 

  • Cammer,W. &Zhang,H. (1992) Carbonic anhydrase in distinct precursors of astrocytes and oligodendrocytes in the forebrains of neonatal and young rats.Dev. Brain Res. 67, 257–63.

    Article  CAS  Google Scholar 

  • Church,G.A.,Kimelberg,H.K. &Sapirstein,V.S. (1980) Stimulation of carbonic anhydrase activity and phosphorylation in primary astroglial cultures by norepinephrine.J. Neurochem. 34, 873–9.

    CAS  PubMed  Google Scholar 

  • Dodgson,S.J. (1987) Inhibition of mitochondrial carbonic anhydrase and ureagenesis: a discrepancy examined.J. Appl. Physiol. 63, 2134–41.

    CAS  PubMed  Google Scholar 

  • Dodgson,S.J.,Forster,R.E. &Storey,B.T. (1984) The role of carbonic anhydrase in hepatocyte metabolism.Ann. NY Acad. Sci. 429, 516–24.

    CAS  PubMed  Google Scholar 

  • Feldstein,J.B. &Silverman,D.N. (1984) Purification and characterization of carbonic anhydrase from the saliva of the rat.J. Biol. Chem. 259, 5447–53.

    CAS  PubMed  Google Scholar 

  • Ghandour,M.S.,Langley,O.K.,Vincendon,G. &Gombos,G. (1979) Double labeling immunohistochemical technique provides evidence of the specificity of glial cell markers.J. Histochem. Cytochem. 27, 1634–7.

    CAS  PubMed  Google Scholar 

  • Ghandour,M.S.,Langley,O.K.,Vincendon,G.,Gombos,G.,Filippi,D.,Limozin,N.,Dalmasso,C. &Laurent,G. (1980) Immunochemical and immunohistochemical study of carbonic anhydrase II in adult rat cerebellum: a marker for oligodendrocytes.Neurosci. 5, 559–71.

    Article  CAS  Google Scholar 

  • Ghandour,M.S.,Langley,O.K.,Zhu,X.L.,Waheed,A. &Sly,W.S. (1992) Carbonic anhydrase IV on brain capillary endothelial cells: A marker associated with the blood-brain barrier.Proc. Natl Acad. Sci. USA 89, 6823–7.

    CAS  PubMed  Google Scholar 

  • Guesdon,J.L.,TernynckT. &Avrameas,S. (1979) The use of avidin-biotin interaction in immunoenzymatic techniques.J. Histochem. Cytochem. 27, 1131–9.

    CAS  PubMed  Google Scholar 

  • Karhukorpi,E.K. (1991) Carbonic anhydrase II in rat acid secreting cells: Comparison of osteoclasts with gastric parietal cells and kidney intercalated cells.Acta Histochem. 90, 11–20.

    CAS  PubMed  Google Scholar 

  • Kimelberg,H.K.,Stieg,P.E. &Mazurkiewicz,J.E. (1982) Immunocytochemical and biochemical analysis of carbonic anhydrase in primary astrocyte cultures from rat brain.J. Neurochem. 39, 734–42.

    CAS  PubMed  Google Scholar 

  • Kleihues,P.,Burger,P.C. &Scheithauer,B.V. (1993) Histological typing of tumours of the central nervous system. In WHOInternational Histological Classification of Tumours, 2nd edn. Weinheim: Springer-Verlag.

    Google Scholar 

  • Korhonen,L.K.,Näätänen,E. &Hyyppä,M. (1964) A histochemical study of carbonic anhydrase in some parts of mouse brain.Acta Histochem. 18, 336–47.

    CAS  PubMed  Google Scholar 

  • Kumpulainen,T. (1984) Immunohistochemical localization of human carbonic anhydrase isozymes.Ann. NY Acad. Sci. 429, 359–68.

    CAS  PubMed  Google Scholar 

  • Kumpulainen,T. &Korhonen,L.K. (1982) Immunohistochemical localization of carbonic anhydrase isoenzyme C in the central and peripheral nervous system of the mouse.J. Histochem. Cytochem. 30, 283–92.

    CAS  PubMed  Google Scholar 

  • Kumpulainen,T. &Nyström,S. (1981) Immunohistochemical localization of carbonic anhydrase isoenzyme C in human brain.Brain Res. 220, 220–5.

    Article  CAS  PubMed  Google Scholar 

  • Kumpulainen,T.,Dahl,D.,Korhonen,L.K. &Nyström,S. (1983) Immunolabeling of carbonic anhydrase isoenzyme C and glial fibrillary acidic protein in paraffin-embedded tissue sections of human brain and retina.J. Histochem. Cytochem. 31, 879–86.

    CAS  PubMed  Google Scholar 

  • Kumpulainen,T.,Rajaniemi,H.,Myllylä,V. &Korhonen,L.K. (1985) A single-step solid phase radioimmunoassay for quantifying human carbonic anhydrase I and II in cerebrospinal fluid.Clin. Chim. Acta 150, 205–12.

    Article  CAS  PubMed  Google Scholar 

  • Laemmli,U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4.Nature 227, 680–5.

    Article  CAS  PubMed  Google Scholar 

  • Murakami,H. &Sly,W.S. (1987) Purification and characterization of human salivary carbonic anhydrase.J. Biol. Chem. 262, 1382–8.

    CAS  PubMed  Google Scholar 

  • Nakagawa,Y.,Perentes,E. &Rubinstein,L.J. (1986) Immunohistochemical characterization of oligodendrogliomas: an analysis of multiple markers.Acta Neuropathol. 72, 15–22.

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa,Y.,Perentes,E. &Rubinstein,L.J. (1987) Non-specifity of anti-carbonic anhydrase C antibody as a marker in human neurooncology.J. Neuropathol. Exp. Neurol. 46, 451–60.

    CAS  PubMed  Google Scholar 

  • Nogradi,A. (1993) Differential expression of carbonic anhydrase isozymes in microglial cell types.GLIA 8, 133–42.

    CAS  PubMed  Google Scholar 

  • Nogradi,A.,Kelly,C. &Carter,N. (1993) Localization of acetazolamide-resistant carbonic anhydrase III in human and rat choroid plexus by immunocytochemistry andin situ hybridisation.Neurosci. Lett. 151, 162–5.

    Article  CAS  PubMed  Google Scholar 

  • Parkkila,S.,Kaunisto,K. &Rajaniemi,H. (1991) Location of the carbonic anhydrase isoenzymes VI and II in human salivary glands by immunohistochemistry. InCarbonic Anhydrase. From Biochemistry and Genetics to Physiology and Clinical Medicine (edited byBotre,F.,Gros,G. &Storey,B.T.), pp. 254–7. Weinheim: VCH Verlagsgesellschaft.

    Google Scholar 

  • Parkkila,A.K.,Parkkila,S.,Juvonen,T. &Rajaniemi,H. (1993a) Carbonic anhydrase isoenzymes II and I are present in the zona glomerulosa cells of the human adrenal gland.Histochemistry 99, 37–41.

    Article  CAS  PubMed  Google Scholar 

  • Parkkila,S.,Parkkila,A.K.,Kaunisto,K.,Waheed,A.,Sly,W.S. &Rajaniemi,H. (1993b) Location of membrane-bound carbonic anhydrase isoenzyme (CA IV) in the human male reproductive tract.J. Histochem. Cytochem. 41, 751–7.

    CAS  PubMed  Google Scholar 

  • Parkilla,S.,Parkkila,A.K.,Vierjoki,T.,St⫗hlberg,T. &Rajaniemi,H. (1993c) Competitive time-resolved immunofluorometric assay for quantifying carbonic anhydrase VI in saliva.Clin. Chem. 39, 2154–7.

    Google Scholar 

  • Parkkila,A.K.,Parkkila,S.,Serlo,W.,Reunanen,M.,Vierjoki,T. &Rajaniemi,H. (1994a) A competitive dual-label time-resolved immunofluorometric assay for simultaneous detection of carbonic anhydrase I and II in cerebrospinal fluid.Clin. Chim. Acta 230, 81–9.

    Article  CAS  PubMed  Google Scholar 

  • Parkkila,S.,Parkkila,A.K.,Juvonen,T. &Rajaniemi,H. (1994b) Distribution of the carbonic anhydrase isoenzymes I, II and VI in the human alimentary tract.Gut 35, 646–50.

    CAS  PubMed  Google Scholar 

  • Parkkila,S.,Parkkila,A.K.,Juvonen,T.,Lehto,V.P. &Rajaniemi,H. (1995) Immunohistochemical demonstration of the carbonic anhydrase isoenzymes I and II in pancreatic tumours.Histochem. J. 27, 133–8.

    CAS  PubMed  Google Scholar 

  • Parthe,V. (1981) Histochemical localization of carbonic anhydrase in vertebrate nervous tissue.J. Neurosci. Res. 6, 119–31.

    CAS  PubMed  Google Scholar 

  • Roussel,G.,Delanoy,J.P.,Nussbaum,J.L.,Mandel,P. (1979) Demonstration of a specific localization of carbonic anhydrase C in the glial cells of rat CNS by an immunohistochemical method.Brain Res. 160, 47–55.

    Article  CAS  PubMed  Google Scholar 

  • Sapirstein,V.S.,Strocchi,P.,Wesolowski,M. &Gilbert,J.M. (1983) Characterization and biosynthesis of soluble and membrane-bound carbonic anhydrase in brain.J. Neurochem. 40, 1251–61.

    CAS  PubMed  Google Scholar 

  • Skaggs,L.A.,Bergenhem,N.C.H.,Venta,P.J. &Tashian,R.E. (1993) The deduced amino acid sequence of human carbonic anhydrase-related protein (CARP) is 98% identical to the mouse homologue.Gene 126, 291–2.

    Article  CAS  PubMed  Google Scholar 

  • Snyder,D.S.,Zimmerman,T.R.,Farooq,M.,Norton,W.T. &Cammer,W. (1983) Carbonic anhydrase, 5′ -nucleotidase and 2′ 3′ -cyclic nucleotide-3′ -phosphodiesterase activities in oligodendrocytes, astrocytes and neurons isolated from the brains of developing rats.J. Neurochem. 40, 120–7.

    CAS  PubMed  Google Scholar 

  • Tashian,R.E. (1989) The carbonic anhydrases: Widening perspectives on their evolution and function.BioEssays 10, 186–92.

    Article  CAS  PubMed  Google Scholar 

  • Tashian,R.E.,Hewett-Emmett,D. &Goodman,M. (1983) On the evolution and genetics of carbonic anhydrases I, II and III. InIsozymes: Current Topics in Biological and Medical Research (edited byRatazzi,M.D.,Scandalios,J.G. &Whitt,G.S.), pp. 79–100. New York: A. R. Liss.

    Google Scholar 

  • Whitney,P.L. &Briggle,T.V. (1982) Membrane-associated carbonic anhydrase purified from bovine lung.J. Biol. Chem. 257, 12056–9.

    CAS  PubMed  Google Scholar 

  • Wistrand,P.J. &Knuuttila,K.-G. (1989) Renal membrane-bound carbonic anhydrase. Purification and properties.Kidney Int. 35, 851–9.

    CAS  PubMed  Google Scholar 

  • Zhu,X.L. &Sly,W.S. (1990) Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney.J. Biol. Chem. 265, 8795–801.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, University of Oulu, FIN-90220, Oulu, Finland

    Anna-Kaisa Parkkila, Seppo Parkkila & Hannu Rajaniemi

  2. Department of Pathology, University of Oulu, FIN-90220, Oulu, Finland

    Riitta Herva

Authors
  1. Anna-Kaisa Parkkila
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Riitta Herva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seppo Parkkila
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hannu Rajaniemi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parkkila, AK., Herva, R., Parkkila, S. et al. Immunohistochemical demonstration of human carbonic anhydrase isoenzyme II in brain tumours. Histochem J 27, 974–982 (1995). https://doi.org/10.1007/BF02389687

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02389687

Keywords

Search

Navigation