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Comparison of bromodeoxyuridine uptake and MIB 1 immunoreactivity in medulloblastomas determined with single and double immunohistochemical staining methods

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Summary

We examined the growth potential of 17 medulloblastomas by single and double immunohistochemical staining with bromodeoxyuridine (BUdR) and MIB 1, a monoclonal antibody for Ki-67 protein, in serial sections of ethanol-fixed, paraffin-embedded tissues; we also assessed the heterogeneity of the immunoreactivity in the tumors. In the most active areas, the BUdR labeling index (LI) was 6.8 to 26.9% (HCl hydrolysis) and 7.5 to 28.8% (microwave heating), and the MIB 1 proliferating cell index (PQ was 14.9 to 56.5%). Linear regression analysis showed that the BUdR LI correlated with the MIB 1 PCI (p < 0.001). The ratio of MIB 1-positive to BUdR-positive cells was 2.2 ± 0.4 by both single and double staining. BUdR-positive nuclei were heterogeneously distributed in all cases, especially in areas with scattered foci of necrosis. Three tumors had areas with many MIB 1-positive but few BUdR-positive nuclei; these areas were associated with recent tumor necrosis. However, in most of the tumors, the densities of BUdR-positive and MIB 1-positive cells changed concomitantly from area to area. These changes were clearly shown by double immunostaining. Thus, transcapillary passage of BUdR does not appear to be impeded in most medulloblastomas. This study suggests that MIB 1 immunostaining provides essentially the same data as BUdR labeling for assessing the proliferative potential of medulloblastomas.

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References

  1. Rorke LB: The cerebellar medulloblastoma and its relationship to primitive neuroectodermal tumors. J Neuropathol Exp Neurol 42: 1–15, 1983

    Google Scholar 

  2. Russell DS, Rubinstein LJ: Pathology of Tumours of the Nervous System (4th edition). Edward Arnold, London, 1977

    Google Scholar 

  3. Hoshino T, Kobayashi S, Townsend JJ, Wilson CB: A cell kinetic study on medulloblastomas. Cancer 55: 1711–1713, 1985

    Google Scholar 

  4. Ito S, Hoshino T, Prados MD, Edwards MSB: Cell kinetics of medulloblastomas. Cancer 70: 671–678, 1992

    Google Scholar 

  5. Giangaspero F, Doglioni C, Rivano MT, Pileri S, Gerdes J, Stein H: Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67. Acta Neuropathol (Berl) 74: 179–182, 1987

    Google Scholar 

  6. Gratzner HG: Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218: 474–475, 1982

    Google Scholar 

  7. Nagashima T, DeArmond SJ, Murovic J, Hoshino T: Immunocytochemical demonstration of S-phase cells by anti-bromodeoxyuridine monoclonal antibody in human brain tumor tissues. Acta Neuropathol (Berl) 67: 155–159, 1985

    Google Scholar 

  8. Molnar P, Groothuis D, Blasberg R, Zaharko D, Owens E, Fenstermacher J: Regional thymidine transport and incorporation in experimental brain and subcutaneous tumors. J Neurochem 43: 421–432, 1984

    Google Scholar 

  9. 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 31: 13–20, 1983

    CAS  PubMed  Google Scholar 

  10. Gerdes J, Lemke H, Baisch H, Wacker H-H, Schwab U; Stein H: Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133: 1710–1715, 1984

    Google Scholar 

  11. Burger PC, Shibata T, Kleihues P: The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology. Am J Surg Pathol 10: 611–617, 1986

    Google Scholar 

  12. Allegranza A, Girlando S, Arrigoni GL, Veronese S, Mauri FA, Gambacorta M, Pollo B, Dalla Palma P, Barbareschi M: Proliferating cell nuclear antigen expression in central nervous system neoplasms. Virchows Arch A Pathol Anat Histopathol 419: 417–423, 1991

    Google Scholar 

  13. Morimura T, Kitz K, Budka H: In situ analysis of cell kinetics in human brain tumors. A comparative immunocytochemical study of S phase cells by a new in vitro bromodeoxyuridine-labeling technique, and of proliferating pool cells by monoclonal antibody Ki-67. Acta Neuropathol (Berl) 77: 276–282, 1989

    Google Scholar 

  14. Shi S-R, Key ME, Kalra KL: Antigen retrieval in formalinfixed, paraffin embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39: 741–748, 1991

    Google Scholar 

  15. Cattoretti G, Becker MHG, Key G, Duchrow M, Schlüter C, Galle J, Gerdes J: Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol 168: 357–363, 1992

    CAS  PubMed  Google Scholar 

  16. Gerdes J, Becker MHG, Key G, Cattoretti G: Immunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues. J Pathol 168: 85–86, 1992

    Google Scholar 

  17. Key G, Becker MHG, Baron B, Duchrow M, Schlüter C, Flad H-D, Gerdes J: New Ki-67-equivalent murine monoclonal antibodies (MIB 1–3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest 68: 629–639, 1993

    Google Scholar 

  18. Onda K, Davis RL, Wilson CB, Hoshino T: Regional differences in bromodeoxyuridine uptake, expression of Ki-67 protein, and nucleolar organizer region counts in glioblastoma multiforme. Acta Neuropathol 87: 586–593, 1994

    Google Scholar 

  19. Dolbeare F, Gratzner H, Pallavicini MG, Gray JW: Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine. Proc Natl Acad Sci USA 80: 5573–5577, 1983

    Google Scholar 

  20. Morstyn G, Hsu S-M, Kinsella T, Gratzner H, Russo A, Mitchell JB: Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody. J Clin Invest 72: 1844–1850, 1983

    Google Scholar 

  21. Shibui S, Hoshino T, Vanderlaan M, Gray JW: Double labeling with iodo- and bromodeoxyuridine for cell kinetics studies. J Histochem Cytochem 37: 1007–1011, 1989

    Google Scholar 

  22. Hayashi Y, Koike M, Matsmani M, Hoshino T: Effects of fixation time and enzymatic digestion on immunohistochemical demonstration of bromodeoxyuridine in formalin-fixed, paraffin-embedded tissue. J Histochem Cytochem 36: 511–514, 1988

    Google Scholar 

  23. Sugihara H, Hattori T, Fukuda M: Immunohistochemical detection of bromodeoxyuridine in formalin-fixed tissues. Histochemistry 85: 193–195, 1986

    Google Scholar 

  24. Watanabe A, Tanaka R, Takeda N, Washiyama K: DNA synthesis, blood flow, and glucose utilization in experimental rat brain tumors. J Neurosurg 70: 86–91, 1989

    Google Scholar 

  25. Tsanaclis AM, Robert F, Michaud J, Brem S: The cycling pool of cells within human brain tumors: in situ cytokinetics using the monoclonal antibody Ki-67. Can J Neurol Sci 18: 12–17, 1991

    Google Scholar 

  26. Deckert M, Reifenberger G, Wechsler W: Determination of the proliferative potential of human brain tumors using the monoclonal antibody Ki-67. J Cancer Res Clin Oncol 115: 179–188, 1989

    Google Scholar 

  27. Onda K, Davis RL, Shibuya M, Wilson CB, Hoshino T: Correlation between the bromodeoxyuridine labeling index and the MIB-1 and Ki-67 proliferating cell indices in cerebral gliomas. Cancer 74: 1921–1926, 1994

    Google Scholar 

  28. Hoshino T, Ito S, Asai A, Shibuya M, Prados MD, Dodson BA, Davis RL, Wilson CB: Cell kinetic analysis of human brain tumors by in situ double labelling with bromodeoxyuridine and iododeoxyuridine. Int J Cancer 50: 1–5, 1992

    Google Scholar 

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Authors and Affiliations

  1. Brain Tumor Research Center of the Department of Neurological Surgery, School of Medicine, University of California, 94143, San Francisco, CA, USA

    Kiyoshi Onda & Michael S.B. Edwards

  2. Department of Pathology School of Medicine, University of California, 94143, San Francisco, CA, USA

    Richard L. Davis

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  1. Kiyoshi Onda
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  2. Richard L. Davis
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  3. Michael S.B. Edwards
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Onda, K., Davis, R.L. & Edwards, M.S. Comparison of bromodeoxyuridine uptake and MIB 1 immunoreactivity in medulloblastomas determined with single and double immunohistochemical staining methods. J Neuro-Oncol 29, 129–136 (1996). https://doi.org/10.1007/BF00182135

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