RETROSPECTIVE STUDY OF THE CORRELATION BETWEEN THE DNA-REPAIR PROTEINALKYLTRANSFERASE AND SURVIVAL OF BRAIN-TUMOR PATIENTS TREATED WITH CARMUSTINE

We tested the hypothesis that the level of the DNA repair protein O-6- alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using mono clonal antibodies against human alkyltransferase. Patients with high l evels of alkyltransferase had shorter time to treatment failure (P = 0 .05) and death (P = 0.004) and a death rate 1.7 times greater than pat ients with low alkyltransferase levels. Furthermore, the size of the s ubpopulation of cells with high levels of alkyltransferase was correla ted directly with drug resistance. For all tumors the variables most c losely correlated with survival, in order of importance, were age, tum or grade, and alkyltransferase levels. For glioblastoma multiforme, su rvival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evalua te alkyltransferase levels as a method for identifying brain tumor pat ients with the best likelihood of response to BCNU chemotherapy.