Flow-cytometric DNA analysis and immunohistochemical measurement of Ki-67 and BUdR labeling indices in human brain tumors

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✓ Cell proliferation potential was assessed by measuring the labeling indices of the monoclonal antibody Ki-67 and of 5-bromodeoxyuridine (BUdR), and the cellular deoxyribonucleic acid (DNA) content in 48 human brain tumors. The diagnostic and prognostic value of flow-cytometric DNA analysis was also evaluated using ethanol-fixed paraffin-embedded BUdR-labeled specimens; these were the same specimens as were used for measuring the BUdR and Ki-67 labeling indices. Both the Ki-67 and the BUdR labeling indices correlated with the degree of malignancy estimated from conventional histological preparations. The Ki-67 labeling index was 1.7 times greater than the BUdR labeling index. The relationship of DNA aneuploidy to the labeling indices or to morphology in cases of glioma was examined. All of the tumors with an aneuploid line corresponded to malignant glioma classified by histological criteria, although malignant glioma did not always show DNA aneuploidy. In addition, the cases with aneuploid lines showed high BUdR and Ki-67 labeling indices. The cell kinetic data, which indicate the biological character of tumors, allowed prediction of the prognosis of the patients with gliomas. In contrast, despite the presence of an aneuploid line, three of 13 meningiomas showed a benign histological pattern without an aggressive clinical course, and neither the Ki-67 nor the BUdR labeling index was high. These results indicate an unequivocal relationship between DNA aneuploidy and clinical behavior; in general, both labeling indices may prove to be objective indicators of the outcome of patients with brain tumors.

Article Information

Address reprint requests to: Takafumi Nishizaki, M.D., Department of Neurosurgery, Yamaguchi University School of Medicine, 1144 Kogushi, Ube-shi, Yamaguchi-ken 755, Japan.

© AANS, except where prohibited by US copyright law.

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Figures

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    Case 11: anaplastic astrocytoma. Upper Left: Photomicrograph of a BUdR preparation with a labeling index of 3.7%. Anti-BUdR stain, × 200. Upper Right: Photomicrograph of a Ki-67 preparation with a labeling index of 4.3%. Ki-67 stain, × 200. Lower: DNA histogram showing an aneuploid line.

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    Distribution of the BUdR labeling index and the histological grading among aneuploid gliomas (open circles) and diploid gliomas (closed circles).

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    Case 20: malignant meningioma. Left: Photomicrograph of a Ki-67 preparation with a labeling index of 7.4%. Ki-67 stain, × 200. Right: DNA histogram showing an aneuploid line.

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    Case 32: transitional-type meningioma. DNA histogram showing an aneuploid line, despite a low Ki-67 labeling index and lack of malignant histological features.

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