Abstract
We tested the hypothesis that the level of the DNA repair protein O6-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 monoclonal antibodies against human alkyltransferase. Patients with high levels 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 patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.
Footnotes
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↵1 This research was supported by a Small Business Innovative Research Prime Contract N44-CM-23760 to Applied Genetics Inc.
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↵2 To whom requests for reprints should be addressed, at Applied Genetics Inc., 205 Buffalo Avenue, Freeport, NY 11520. Phone: (516) 868-9026; Fax: (516) 868-9143.
- Received October 4, 1995.
- Accepted December 12, 1995.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 4
