Cell kinetic classification of tumors of the nervous system by DNA precursor labeling in vitro

We studied 142 excisional or needle biopsy specimens of nervous system tumors with tritiated thymidine or 5'-bromodeoxyuridine (BrdUrd). Either precursor gave similar results. A labeling index (LI), expressed as a percentage and representing the S-phase fraction, was measured by a microscopic count from stained sections. The in vitro method ranked mean and median LIs of different neoplasms similarly to reported results from the in vivo administration of BrdUrd and reflected clinical aggressiveness of various tumor types. Gliosis, myxopapillary ependymomas, benign meningiomas, neurilemmomas, and pituitary adenomas consistently showed LIs less than 1%. The LI of a cerebellar Lhermitte-Duclos gangliocytoma was zero, indicating the virtual absence of proliferation. Mean LIs and standard deviations of other tumors were as follows: anaplastic astrocytomas, 3.07% +/- 2.98%; glioblastoma multiforme, 6.15% +/- 5.61%; non-Hodgkin's lymphoma, 12% +/- 9.5%; and metastatic neoplasms, 15% +/- 8.5%. The survival rate of patients with astrocytic tumors was inversely proportional to the LI. We conclude that the in vitro method is a practical alternative to in vivo BrdUrd administration for measurement of S-phase cells in tumors of the nervous system that gives prognostically useful information. Combination of BrdUrd LI with growth fraction measurement by monoclonal antibodies could offer new insights into brain tumor cell kinetics.