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The Cycling Pool of Cells within Human Brain Tumors: In Situ Cytokinetics Using the Monoclonal Antibody Ki-67

Published online by Cambridge University Press:  18 September 2015

Ana Maria Tsanaclis
Affiliation:
Lady Davis Institute for Medical Research and the Department of Neuroscience, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec Department of Neurology and Neurosurgery, McGill University, Montréal, Québec
Françoise Robert
Affiliation:
Department of Pathology, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec Department of Pathology, University of Montréal, Montréal, Québec
Jean Michaud
Affiliation:
Department of Pathology, Ste. Justine Hospital, Montréal, Québec Department of Pathology, University of Montréal, Montréal, Québec
Steven Brem*
Affiliation:
Lady Davis Institute for Medical Research and the Department of Neuroscience, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec Department of Oncology, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec Department of Neurology and Neurosurgery, McGill University, Montréal, Québec
*
Neurosurgical Oncology, 233 East Erie Street, Suite 500, Chicago, Illinois, U.S.A. 60611-2906
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Abstract:

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Brain tumor growth results from the relative proportion of cells contained in three populations: a) cycling/proliferative; b) quiescent (Go)/static, and c) terminally differentiated/dying. The cycling compartment can be detected by the mouse monoclonal Ki-67 antibody, an available, rapid, safe, sensitive, and specific method for immunostaining of proliferative cells. We report the Ki-67 labeling index (LI) in 48 brain tumors. Malignant brain tumors have elevated Lis, ranging from 6.0% to 56.9%: anaplastic astrocytoma, 8.0 ± 7.3; glioblastoma multiforme, 10.1 ±4.2; germinoma, 11.7; medulloblastoma, 13.1 ± 6.6; metastases, 40.3 ± 13.1. By contrast, slow-growing tumors showed lower values (P < .001), approaching 1%: acoustic schwannoma, 0.4 ± 0.6; pituitary adenoma, 1.3 ± 1.9; meningioma, 1.2 ± 1.2; low-grade astrocytoma, < 1; pilocytic astrocytoma, 5.6. Human brain tumors can therefore be ranked according to the percentage of cycling cells with the acoustic schwannoma among the least proliferative and the metastatic carcinoma among the most proliferative. Within a given histotype, the Ki-67 LI may have prognostic and therapeutic implications for the individual patient. Already important for neuro-oncology research, the Ki-67 labeling index should be added to the armamentarium of the clinical neuropathologist to complement the standard histopathologic diagnosis with a cytokinetic analysis of cellular proliferation.

Type
Original Articles
Copyright
Copyright © Canadian Neurological Sciences Federation 1991

References

1.Rosenblum, ML, Berens, ME, Rutka, JT. Recent perspectives in brain tumor biology and treatment. Clin Neurosurg 1989; 35: 314335.Google ScholarPubMed
2.Tannock, IF. Tumor growth and cell kinetics. In: Tannock, IF, Hill, RP, (editor). The Basic Science of Oncology. New York, Pergamon Press, 1987; 140159.Google Scholar
3.Baserga, R. The cell cycle. N Engl J Med 1981; 304: 453459.CrossRefGoogle ScholarPubMed
4.Hoshino, T. A commentary on the biology and growth kinetics of lowgrade and high-grade gliomas. J Neurosurg 1984; 61: 895900.CrossRefGoogle ScholarPubMed
5.Hoshino, T, Wilson, CB, Rosenblum, ML, et al. Chemotherapeutic implications of growth fraction and cell cycle time in glioblastomas. J Neurosurg 1975; 43: 127135.CrossRefGoogle ScholarPubMed
6.Hoshino, T, Wilson, CB. Cell kinetic analysis of human malignant brain tumors (gliomas). Cancer 1979; 44: 956962.Google ScholarPubMed
7.Hoshino, T, Rodriguez, LA, Cho, KG, et al. Prognostic implications of the proliferative potential of low-grade astrocytomas. J Neurosurg 1988; 839842.CrossRefGoogle ScholarPubMed
8.Brien, SE, Zagzag, D, Brem, S. Rapid in situ cellular kinetics of intracerebral tumor angiogenesis using a monoclonal antibody to bromodeoxyuridine. Neurosurgery 1989; 25: 715719.CrossRefGoogle ScholarPubMed
9.Yoshii, Y, Maki, Y, Tsuboi, K, et al. Estimation of growth fraction with bromodeoxyuridine in human central nervous system tumors. J Neurosurg 1986; 65: 659663.Google ScholarPubMed
10.Murovic, JA, Nagashima, T, Hoshino, T, et al. Pediatric central nervous system tumors: A cell kinetic study with bromodeoxyuridine. Neurosurgery 1986; 19: 900914.CrossRefGoogle ScholarPubMed
11.Gerdes, J, Lemke, H, Baisch, H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984; 133: 17101715.CrossRefGoogle ScholarPubMed
12.Gerdes, J. An immunohistological method for estimating cell growth fractions in rapid histopathological diagnosis during surgery. Int J Cancer 1985; 35: 169171.CrossRefGoogle ScholarPubMed
13.Lellé, RJ, Heidenreich, W, Stauch, G, et al. The correlation of growth fractions with histologic grading and lymph node status in human mammary carcinoma. Cancer 1987; 59: 8388.Google ScholarPubMed
14.Sasaki, K, Matsumura, K, Tsuji, T, et al. Relationship between labeling indices of Ki-67 and BrdUrd in human malignant tumors. Cancer 1988; 62: 989993.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
15.Nishizaki, T, Orita, T, Furutani, Y, et al. Flow-cytometric DNS analysis and immunohistochemical measurement of Ki-67 and BUdR labeling indices in human brain tumors. J Neurosurg 1989; 70: 379384.CrossRefGoogle Scholar
15.Schwartz, BR, Pinkus, G, Bacus, S, et al. Cell proliferation in non-Hodgkin’s lymphomas: Digital image analysis of Ki-67 antibody staining. Am J Pathol 1989; 134: 327336.Google ScholarPubMed
17.Burger, PC, Shibata, T. The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: Application to surgical neuropathology. Am J Surg Pathol 1986; 10: 611617.CrossRefGoogle ScholarPubMed
18.Knosp, E, Kitz, K, Pemeczky, A. Proliferation activity in pituitary adenomas: Measurement by monoclonal antibody Ki-67. Neurosurgery 1989; 25: 927930.CrossRefGoogle ScholarPubMed
19.Patsouris, E, Stocker, U, Kallmeyer, V,et al Relationship between Ki-67 positive cells, growth rate and histological type of human intracranial tumors. Anticancer Res 1988; 8: 537544.Google ScholarPubMed
20.Zuber, P, Hamou, M-F, de Tribolet, N,et al. Identification of proliferating cells in human gliomas using the monoclonal antibody Ki-67. Neurosurgery 1988; 22: 364368.CrossRefGoogle ScholarPubMed
21.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 1989; 115: 179188.Google ScholarPubMed
22.Giangaspero, F, Doglioni, C, Rivano, MT, et al. Growth fractions in human brain tumors defined by the monoclonal antibody Ki-67. Acta Neuropathol (Berl) 1987; 74: 179182.CrossRefGoogle ScholarPubMed
23.Roggendorf, W, Shuster, T, Peiffer, J. Proliferation potential of meningiomas determined with the monoclonal antibody Ki-67. Acta Neuropathol (Berl) 1987; 73: 361364.CrossRefGoogle ScholarPubMed
24.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 vino bromodeoxyuridine-labeling technique, and of proliferating pool cells by monoclonal antibody Ki-67. Acta Neuropathol 1989; 77: 276282.Google Scholar
25.Raghavan, R, Steart, PV, Weller, RO. ICell proliferation patterns in the diagnosis of astrocytomas, anaplastic astrocytomas and glioblastoma multiforme: a Ki-67 study. Neuropathol Appl Neurobiol 1990; 16: 123133.CrossRefGoogle Scholar
26.Shepherd, NA, Richman, PI, England, J. IKi-67 derived proliferative activity in colorectal adenocarcinomas with prognostic correlations. J Pathol 1988; 155: 213219.Google Scholar
27.Kaudewitz, P, Braun-Falco, O, Ernst, M, et al. Tumor cell growth fractions in human malignant melanomas and the correlation to histopathologic tumor grading. Am J Pathol 1989; 134: 10631068.Google ScholarPubMed
28.Verheijen, R, Kuijpers, HJH, Schlingemann, RO, et al. Ki-67 detects a nuclear matrix-associated proliferation-related antigen. I.Intracellular localization during interphase. J Cell Sci 1989; 92: 123130.Google ScholarPubMed
29.Guillaud, P, du Manoir, S, Seigneurin, D. Quantification and topographical description of Ki-67 antibody labelling during the cell cycle of normal fibroblastic (MRC-5) and the mammary tumor cell lines (MCF-7). Anal Cell Pathol 1989; 1: 2539.Google ScholarPubMed
30.Russell, DS, Rubinstein, JL(editor). Pathology of Tumors of the Nervous System; (editor). Baltimore: Williams and Wilkins, 1989.Google Scholar
31.Sasaki, K, Murakami, T, Kawasaki, M, et al. The cell cycle associated change of the Ki-67 reactive nuclear antigen expression. J Cell Physiol 1987; 133: 579584.Google ScholarPubMed
32.Falini, B, Flenghi, L, Fagioli, M, et al. Evolutionary conservation in various mammalian species of the human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody. J Histochem Cytochem 1989; 37: 14711478.CrossRefGoogle ScholarPubMed
33.Verheijen, R, Kuijpers, HJH, van Driel, R, et al. Ki-67 detects a nuclear matrix-associated proliferation-related antigen. II. Localization in mitotic cells and association with chromosomes. J Cell Sci 1989; 92: 531540.CrossRefGoogle ScholarPubMed
34.Wylie, AH. The biology of cell death in tumors. Anticancer Res 1985; 5: 131136.Google Scholar
35.Kerr, KM, Lamb, D. Actual growth rate and tumor cell proliferation in human pulmonary neoplasms. Br J Cancer 1984; 50: 343349.CrossRefGoogle ScholarPubMed
36.Wang, E, Krueger, JG. Application of a unique monoclonal antibody as a marker for nonproliferating subpopulations of cells of some tissue. J Histochem Cytochem 1985; 65: 537594.Google Scholar
37.McKeever, PE, Feldenzer, JA, McCoy, JP, et al. Nuclear parameters as prognostic indicators in glioblastoma patients. J Neuropathol Exp Neurol 1990; 49: 7178.CrossRefGoogle ScholarPubMed
38.Reifenberger, G, Deckert, M, Wechsler, W. Immunohistochemical determination of protein kinase C expression and proliferative activity in human brain tumors. Acta Neuropathol 1989; 78: 166175.Google ScholarPubMed
39.Hoshino, T, Nagashima, T, Cho, KG. Variability in the proliferative potential of human gliomas. J Neuro-Oncol 1989; 7: 137143.CrossRefGoogle ScholarPubMed
40.Brem, S, Tsanaclis, AMC, Zagzag, D. Anticopper treatment inhibits pseudopodial protrusion and the invasive spread of 9L gliosarcoma cells in the rat brain. Neurosurgery 1990; 26: 391396.CrossRefGoogle ScholarPubMed