Growth fraction of human central nervous system tumors measured by using bromodeoxyuridine.

Abstract

The growth fraction (GF) of brain tumors in 26 patients was estimated by counting the nuclei that incorporated fractionated doses of 200 mg/sq m of bromodeoxyuridine (BrdU) injected every 8 hours for 3 days prior to surgery. Each tumor section embedded in paraffin was reacted with monoclonal antibodies against BrdU and visualized by means of immunoperoxidase. To estimate the GF of each tumor, the areas containing histologically viable tumor cells were selected. The BrdUlabeled cells were scored in 3 to 6 microscopic fields for totals of 1, 000 to 2, 000 tumor cell populations. GF was expressed by a ratio of the BrdU-labeled cells divided by total cells counted. GFs were 9.1 to 46.5% in malignant gliomas, 2.0 to 24.8% in benign gliomas, 11.2 to 43.2% in central nervous system metastasis, 6.2 to 8.2% in meningioma, 3.9 to 4.6% in acoustic neurinoma, 0.8 to 1.9% in pituitary adenoma, and 6.1 % in cerebellar hemangioblastoma. Average GFs of glioblastoma multiforme, giant cell glioblastoma, and astrocytoma grade IV were approximately 32%, whereas those of low grade astrocytoma and oligodendroglioma were 5%. In addition, the average intervals between onset of initial neurological signs and surgery, or relapse and surgery, were 3 months in malignant glioma and central nervous system metastasis, and were over 12 months in benign brain tumors including low grade glioma, meningioma, and acoustic neurinoma. Therefore, GFs estimated by this method appear to correlate with the biologically malignant nature of each human brain tumor in situ.