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Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignany and proliferation indices

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Summary

Proliferation indices and mean number of silver-stained nucleolar organizer region-associated proteins (Ag-NORs) are compared in 65 brain tumors, including 34 gliomas, 8 meningiomas, 17 metastatic tumors, and 6 other tumors. Immunocytochemical investigations include labeling with the monoclonal antibody Ki-67 which identifies the whole growth fraction, and with a monoclonal antibody against bromodeoxyuridine (BrdUrd) which detects cells in the S phase of the cell cycle after in vitro incubation with BrdUrd. When all types of tumors are collectively considered, mean numbers of Ag-NORs did not correlate with Ki-67 and Brd-Urd labeling indices (LIs) and mitotic index. Among tumor subtypes, only meningiomas showed significant correlations between Ag-NOR counts, LIs, and malignancy. Mean number of Ag-NORs did not correlate with proliferation indices and tumor grade in low-grade and high-grade gliomas. However, recurrent high-grade gliomas showed a tendency to higher Ag-NOR counts than primary tumors. This study indicates that counting of Ag-NORs in paraffin sections is of limited value in tumor neuropathology. Correlations found in meningeal tumors should be substantiated in larger series.

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References

  1. Ashworth MT, Helliwell TR (1988) Nucleolar organizer regions in benign, dysplastic and malignant laryngeal squamous epithelium (abstract). J Pathol 154:64A

    Google Scholar 

  2. Bloom SE, Goodpasture C (1976) An improved technique for silver staining of nucleolar organizer regions in human chromosomes. Hum Genet 34:199–206

    Google Scholar 

  3. Burger PC, Shibata T, Kleihues P (1986) 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

    Google Scholar 

  4. Cibull ML, Heryet A, Gatter KC, Mason DY (1989) The utility of Ki-67 immunostaining, nucleolar organizer region counting, and morphology in the assessment of follicular lymphomas. J Pathol 158:189–193

    Google Scholar 

  5. Crocker J, Egan MJ (1988) Correlation between NOR sizes and numbers in non-Hodgkin's lymphomas. J Pathol 156:233–239

    Google Scholar 

  6. Crocker J, Nar P (1987) Nucleolar organizer regions in lymphomas. J Pathol 151:111–118

    Google Scholar 

  7. Crocker J, Skilbeck N (1987) Nucleolar organizer region associated proteins in cutaneous melanotic lesions: a quantitative study. J Clin Pathol 40:885–889

    Google Scholar 

  8. Crocker J, Ayres J, McGovern J (1987) Nucleolar organizer regions in small cell carcinoma of the bronchus. Thorax 42:972–975

    Google Scholar 

  9. Crocker J, Ayres JG, Stilbeck NQ (1988) Evaluation of the Ag-NOR technique in the diagnosis of malignant mesotheliomas (abstract) J Pathol 154:43A

    Google Scholar 

  10. Crocker J, Macartney JC, Smith PJ (1988) Correlation between DNA flow cytometric and nucleolar organizer region data in non-Hodgkin's lymphomas. J Pathol 154:151–156

    Google Scholar 

  11. Crocker J, Boldy DAR, Egan MJ (1989) How should we count Ag-NORs? Proposals for a standardized approach. J Pathol 158:185–188

    Google Scholar 

  12. Derenzini M, Betts CM, Ceccarelli C, Eusebi V (1986) Ultrastructural organization of nucleoli in benign naevi and malignant melanomas. Virchows Arch [B] 52:343–352

    Google Scholar 

  13. Derenzini M, Farabegoli F, Pession A, Novello F (1987) Spatial redistribution of ribosomal chromatin in the fibrillar centres of human lymphocytes after stimulation of transcription. Exp Cell Res 170:31–41

    Google Scholar 

  14. Derenzini M, Romagnoli T, Mingazzini P, Marinozzi V (1988) Interphasic nucleolar organizer region distribution as a diagnostic parameter to differentiate benign from malignant epithelial tumors of human intestine. Virchows Arch [B] 54:334–340

    Google Scholar 

  15. Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20

    Google Scholar 

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

    Google Scholar 

  17. Giri DD, Nottingham JF, Lawry J, Dundas SAC, Underwood JCE (1989) Silver-binding nucleolar organizer regions (Ag-NORs) in benign and malignant breast lesions: correlations with ploidy and growth phase by DNA flow cytometry. J Pathol 157: 307–313

    Google Scholar 

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

    Google Scholar 

  19. Hall PA, Crocker J, Watts A, Stansfeld AG (1988) A comparison of nucleolar organizer region staining and Ki-67 immuno-staining in non-Hodgkin's lymphoma. Histopathology 12:373–381

    Google Scholar 

  20. Hernandez-Verdun D, Derenzini M, Bouteille M (1982) The morphological relationship in electron microscopy between NOR-silver proteins and intranucleolar chromatin. Chromosoma 85:461–473

    Google Scholar 

  21. Hoshino T, Nagashima T, Murovic JA, Wilson CB, Davis RL (1986) Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine. Cancer 58:1466–1472

    Google Scholar 

  22. Hoshino T, Prados M, Wilson CB, Davis RL (1989) Survival of patients with gliomas correlated with bromouriding labeling index (BUdR-LI) of individual tumors (abstract). J Neuropathol Exp Neurol 48:303

    Google Scholar 

  23. Howat AJ, Giri DD, Wright AL, Underwood JCE (1988) Silverstained nucleoli and nucleolar organizer region counts are of no prognostic value in thick cutaneous malignant melanoma. J Pathol 156:227–232

    Google Scholar 

  24. Hsu S-M, Raine L, Fanger H (1981) Use of avidin-biotinperoxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580

    Google Scholar 

  25. Hubbell HR, Hsu TC (1977) Identification of nucleolus organizer regions (NORs) in normal and neoplastic human cells by the silver-staining technique. Cytogenet Cell Genet 19: 185–196

    Google Scholar 

  26. Kernohan JW, Mabon RF, Svien HJ, Adson AW (1949) Symposium on a new and simplified concept of gliomas (a simplified classification of the gliomas). Proc Mayo Clin 24:71–75

    Google Scholar 

  27. Leong A S-Y, Gilham P (1989) Silver staining of nucleolar organizer regions in malignant melanoma and melanotic nevi. Hum Pathol 20:257–262

    Google Scholar 

  28. Love R, Takeda M, Soriano RZ, McCullough LB (1973) The value of the internal structure of the nucleolus in the diagnosis of malignancy. Acta Cytol 17:310–315

    Google Scholar 

  29. Maier H, Morimura T, Hallbrucker C Öfner D, Kitz K, Budka H (1989) Argyrophilic nucleolar organizer regions (Ag-NORs) in human brain tumors: correlation with grade of malignancy and with proliferation indices (abstract). Clin Neuropathol 8:240–241

    Google Scholar 

  30. McNicol AM, Colgan J, McMeekin W, Teasdale GM (1989) Nucleolar organizer regions in pituitary adenomas. Acta Neuropathol 77:547–549

    Google Scholar 

  31. Morimura T, Kitz K, Budka H (1989) In situ analysis of cell kinetics in human brai 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 77:276–282

    Google Scholar 

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

    Google Scholar 

  33. Nishizaki T, Orita T, Saiki M, Furutani Y, Aoki H (1988) Cell kinetics studies of human brain tumors by in vitro labeling using anti-BUdR monoclonal antibody. J Neurosurg 69:371–374

    Google Scholar 

  34. Nishizaki T, Orita T, Furutani Y, Ikeyama Y, Aoki H, Sasaki K (1989) Flow-cytometric DNA analysis in immunohistochemical measurement of Ki-67 and BUdr labeling indices in human brain tumors. J Neurosurg 70:379–384

    Google Scholar 

  35. Öfner D, Tötsch M, Sandbichler P, Hallbrucker C, Margreiter R, Mikuz G, Schmid KW (1990) Silver stained nucleolar organizer region proteins (Ag-NORs) as a predictor of prognosis in colonic cancer. J Pathol (in press)

  36. Ostertag CB, Volk B, Shibata T, Burger P, Kleihues P (1987) The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumors. Acta Neurochir (Wien) 89:117–121

    Google Scholar 

  37. Plate KH, Rüschoff J, Behnke J, Mennel HD (1989) Correlation of silver stained nucleolar organizer regions (Ag-NORs) with malignancy grade and Ki-67 labeling index in smear preparations of human CNS neoplasms (abstract). Clin Neuropathol 8:245–246

    Google Scholar 

  38. Ploton D, Menager M, Jeannesson P, Himber G, Pigeon F, Adnet J-J (1986) Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level. Histochem J 18:5–14

    Google Scholar 

  39. Roggendorf W, Schuster T, Pfeiffer J (1987) Proliferative potential of meningiomas determined with the monoclonal antibody Ki-67, Acta Neuropathol (Berl) 73:361–364

    Google Scholar 

  40. Rüschoff J, Plate KH, Bittinger A (1989) Application of the Ag-NOR method to cell imprints. J Pathol 158:333

    Google Scholar 

  41. Sasaki K, Ogino T, Takahashi M (1986) Immunological determination of labeling index on human brain tumor tissue sections using monoclonal anti-BrdUrd antibody. Stain Technol 61:155–161

    Google Scholar 

  42. Sasaki K, Matsumura K, Tsuji T, Shinozaki F, Takahashi M (1988) Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors. Cancer 62:989–993

    Google Scholar 

  43. Smith R, Crocker J (1988) Evaluation of nucleolar organizer region-associated proteins in breast malignancy. Histopathology 12:113–125

    Google Scholar 

  44. Underwood JCE, Giri DD (1988) Nucleolar organizer regions as diagnostic discriminants for malignancy. J Pathol 155:95–96

    Google Scholar 

  45. Zankl H, Huwer H, Zang KD (1982) Cytogenetic studies on the nucleolar organizer region (NOR) activity in meningloma cells with normal and hypodiploid karyotypes. Cancer Genet Cytogenet 6:47–53

    Google Scholar 

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Maier, H., Morimura, T., Öfner, D. et al. Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignany and proliferation indices. Acta Neuropathol 80, 156–162 (1990). https://doi.org/10.1007/BF00308919

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  • DOI: https://doi.org/10.1007/BF00308919

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