The cycling pool of cells within human brain tumors: in situ cytokinetics using the monoclonal antibody Ki-67.

Abstract

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 less than .001), approaching 1%: acoustic schwannoma, 0.4 +/- 0.6; pituitary adenoma, 1.3 +/- 1.9; meningioma, 1.2 +/- 1.2; low-grade astrocytoma, less than 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.