Abstract
The distribution of proliferating cell nuclear antigen (PCNA)-(clone PC 10)- and Ki-67- (clone MIB-1)-positive nuclei was investigated in 60 medulloblastomas of childhood. Although the labeling index of the two markers did not coincide, both showed a wide range of parallel variations. The percentage of positive nuclei was similar in both classic and desmoplastic tumors. A variable proliferation capacity was found in the different tumor structures. Areas with neuronal and glial differentiation showed very few positive nuclei; these were very abundant in the infiltration areas, and along penetrating vessels from subarachnoidal growths. Pale islands were negative or positive only in their peripheral part. Large-cell areas were richer in positive nuclei than classic ones, accounting for their more malignant character. Hyperchromatic round nuclei, not belonging to necrotic foci and called lymphocyte-like nuclei, differently interpreted in the past, were vairiably found in every case. They are known, from previous experience, to stain orange with Acridine Orange fluorochroming, like single-stranded DNA. They were not easily distinguishable from mitoses and were stained by in situ end-labeling of DNA strand breaks, as demonstrated by incorporation of labeled nucleotides. They were regarded as possible apoptotic nuclei, representing either a peculiar type of cell death or the preservation of the cell deletion capacity, typical of the embryonal tissue of origin.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Allegranza A, Girlando S, Arrigoni GL, Veronese S, Mauri FA, Gambacorta M, Pollo B, Dalla Palma P, Barbareschi M (1991) Proliferating cell nuclear antigen expression in central nervous system neoplasms. Virchows Arch [A] 419: 417–423
Burger PC, Shibata C, 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
Burger PC, Scheithauer BW, Vogel FS (1991) Surgical pathology of the nervous system and its coverings, 3rd edn. Churchill Livingstone, New York, pp 737
Caputy AJ, McCullough DC, Manz HJ, Patterson K, Hammock MK (1987) A review of the factors influencing the prognosis of medulloblastoma. The importance of cell differentiation. J Neurosurg 66: 80–87
Cattoretti G, Becker MHG, Key G, Duchrow M, Schlüter C, Galle J, Gerdes J (1992) Monoclonal antibodies against recombinant part 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
Chatty EM, Earle KM (1971) Medulloblastoma. A report of 201 cases with emphasis on the relationship of histologic variants to survival. Cancer 28: 977–983
Cotter TG, Lennon SV, Glynn JG, Martin SJ (1990) Cell death via apoptosis and its relationship to growth. Development and differentiation of both tumour and normal cells. Anticancer Res 10: 1153–1160
Darzynkiewicz Z, Bruno S, Del Bino G, Gorczyca W, Hotz MA, Lassota P, Traganos F (1992) Features of apoptotic cells measured by flow cytometry. Cytometry 13: 795–808
Gavrieli Y, Sherman Y, Ben Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119: 493–501
Giangaspero F, Rigobello L, Badiali M, Loda M, Andreini L, Basso G, Zorzi F, Montaldi A (1992) Large-cell medulloblastoma. A distinct variant with aggressive behavior. Am J Surg Pathol 16: 687–693
Giordana MT, Cavalla P, Chiò A, Marino S, Vigliani MC, Schiffer D (1993) Usefulness of Ki-67, Clone MIB-1, as a prognostic factor in ependymomas (abstract). J Neuropathol Exp Neurol 52: 324
Goldberg-Stern H, Gadoth N, Stern S, Cohen IJ, Zaizov R, Sandbank U (1991) The prognostic significance of glial fibrillary acidic protein staining in medulloblastoma. Cancer 68: 568–573
Hall PA, Levison DA (1990) Review: assessment of cell proliferation in histological material. J Clin Pathol 43: 184–192
Herpers MJHM, Budka H (1985) Primitive neuroectodermal tumors including the medulloblastoma: glial differentiation signaled by immunoreactivity for GFAP is restricted to the pure desmoplastic medulloblastoma (“arachnoidal sarcoma of the cerebellum”). Clin Neuropathol 4: 12–18
Hubbard JL, Scheithauer BW, Kispert DB, Carpenter SM, Wick MR, Laws ER (1989) Adult cerebellar medulloblastomas: the pathological, radiographic, and clinical disease spectrum. J Neurosurg 70: 536–544
Ito S, Hoshino T, Prados MD, Edwards MSB (1992) Cell kinetics of medulloblastomas. Cancer 70: 671–678
Jaros E, Perry RH, Adam L, Kelly PJ, Crawford PJ, Kalbag PRM, Mendelow AD, Sengupta RP, Pearson ADJ (1992) Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labeling in brain tumours. Br J Cancer 66: 373–385
Karamitopoulou E, Perentes E, Melachrinou M, Maraziotis T (1993) Proliferating cell nuclear antigen immunoreactivity in human central nervous system neoplasms. Acta Neuropathol 85: 316–322
Karamitopoulou E, Perentes E, Diamantis I (1993) Ki-67 immunoreactivity in human central nervous system tumors. A retrospective study with MIB 1 monoclonal antibody (abstract). J Neuropathol Exp Neurol 52: 290
Katsetos CD, Lin HM, Zacks SI (1988) Immunohistochemical and ultrastructural observations on Homer-Wright (neuroblastic) rosettes and the “pale islands” of human cerebellar medulloblastomas. Hum Pathol 19: 1219–1227
Key G, Becker MHG, Duchrow M, Schluter C, Gerdes J (1992) New Ki-67 equivalent murine monoclonal antibodies (MIB 1–3) prepared against recombinant parts of the Ki-67 antigen. Anal Cell Pathol 4: 181
Kopelson G, Linggood R, Kleinman G (1983) Medulloblastoma: the identification of prognositic subgroups and implications for multimodality management. Cancer 51: 312–319
Kurki P, Vanderlaan M, Dolbeare F, Gray J, Tan EM (1986) Expression of proliferating cell nuclear antigen (PCNA)/cycling during the cell cycle. Exp Cell Res 166: 209–219
Maire JP, Guérin J, Rivel J, San Galli F, Bernard C, Dautheribes M, Caudry M (1992) Le médulloblastome de l'enfant. Incidence pronostique de l'hyperplasie vasculaire, de la nécrose de coagulation et de l'état clinique post-opératoire sur la survie. Neurochirurgie 38: 80–88
Morimura T, Kitz K, Budka H (1989) 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 77: 276–282
Morimura T, Kitz K, Stein H, Budka H (1991) Determination of proliferative activities in human brain tumor specimens: a comparison of three methods. J Neurooncol 10: 1–11
Packer RJ, Sutton LN, Rorke LB, Littmann PA, Sposto R, Rosenstock JG, Bruce DA, Schut L (1984) Prognostic importance of cellular differentiation in medulloblastoma of childhood. J Neurosurg 61: 296–301
Penfield W (1932) Cytology and cellular pathology of the nervous system, vol 3. Hoeber, New York, pp 1221–1237
Raghavan R, Steart PV, Weller RO (1990) Cell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study. Neuropathol Appl Neurobiol 16: 123–133
Revesz T, Alsanijari N, Darling JL, Scaravilli F, Lane DP, Thomas DGT (1993) Proliferating cell nuclear antigen (PCNA): expression in samples of human astrocytic gliomas. Neuropathol Appl Neurobiol 19: 152–158
Ringertz N (1955) On the question of different histologic types of medulloblastoma. Proceedings of the 3rd. International Congress on Neuropathology, London 1955. Excerpta Med Sect VIII, Neurol Psichiat 8: 820–821
Ringertz N, Tola JH (1950) Medulloblastoma. J Neuropathol Exp Neurol 9: 354–372
Roussy G, Oberling CH (1932) Atlas du Cancer. Alcan, Paris
Scaravilli F, Duchen LW (1980) Electron microscopic and quantitative studies of cell necrosis in developing sensory ganglia in normal and Sprawling mutant mice. J Neurocytol 9: 373–380
Schiffer D, Fabiani A, Monticone GF, Cognazzo A (1966) On the nature of the lymphocyte-like cells of medulloblastomata. Acta Neuropathol (Berl) 6: 290–297
Schiffer D, Giordana MT, Vigliani MC (1990) Brain tumors of childhood. Nosological and diagnostic problems. Childs Nerv Syst 5: 220–229
Schiffer D, Chio A, Giordana MT, Pezzulo T, Vigliani MC (1993) Proliferating cell nuclear antigen expression in brain tumors, and its prognostic roles in ependymomas: an immunohistochemical study. Acta Neuropathol 85: 495–502
Wijsman JH, Jonker RR, Keijzer R, Van de Velde CJH, Cornelisse CJ, van Dierendonck JH, (1993) A new method to detect apoptosis in parafin sections: in situ end-labeling of fragmented DNA. J Histochem Cytochem 41: 7–12
Wyllie AH, Morris RG, Smith AL, Dunlop D (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 142: 67–77
Yagishita S, Itoh Y, Chiba Y, Kuvana N (1982) Morphological investigations on cerebellar “neuroblastoma” group. Acta Neuropathol (Berl) 56: 22–28
Zuber P, Hamou M-F, de Tribolet N (1988) Identification of proliferating cells in human gliomas using the monoclonal antibody Ki-67. Neurosurgery 22: 364–368
Zülch KJ (1956) Biologie und Pathologie der Hirngeschwülste. In: Handbuch der Neurochirurgie, vol 3. Springer-Verlag, Berlin Göttingen Heidelberg, pp 800
Author information
Authors and Affiliations
Additional information
Supported by AIRC, Milan and CNR, A. C. R. O.-Grant no. 9202191
Rights and permissions
About this article
Cite this article
Schiffer, D., Cavalla, P., Chiò, A. et al. Tumor cell proliferation and apoptosis in medulloblastoma. Acta Neuropathol 87, 362–370 (1994). https://doi.org/10.1007/BF00313605
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00313605