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[Cancer Research 56, 783-788, February 15, 1996]
© 1996 American Association for Cancer Research
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Retrospective Study of the Correlation between the DNA Repair Protein Alkyltransferase and Survival of Brain Tumor Patients Treated with Carmustine1

Michael Belanich, Monica Pastor, Terri Randall, Denise Guerra, Jeannie Kibitel, Lori Alas, Ben Li, Marc Citron, Patricia Wasserman, Agnes White, Harmon Eyre, Kurt Jaeckle, Susan Schulman, Dori Rector, Michael Prados, Stephen Coons, William Shapiro and Daniel Yarosh2

Applied Genetics Inc., Freeport, New York 11520 [M. B., M. Pa., T. R., D. G., J. K., L. A., D. Y.]; Institute of Molecular and Cellular Biology, University of Singapore, 0511 Singapore [B. L.]; Section of Medical Oncology, Department of Hematology/Oncology, Long Island Jewish Medical Center, New Hyde Park, New York 11042 [M. C., P. W., A. W.]; Medical Affairs & Research, American Cancer Society, Atlanta, Georgia 30329 [H. E.]; Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [K. J.]; Huntsman Cancer Institute, The University of Utah, Salt Lake City, Utah [S. S.]; Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington [D. R.]; Brain Tumor Research Institute, University of California, San Francisco, San Francisco, California [M. Pr.]; and Barrows Neurological Institute, St. Joseph's Hospital, Phoenix, Arizona [S. C., W. S.]

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.

1 This research was supported by a Small Business Innovative Research Prime Contract N44-CM-23760 to Applied Genetics Inc.

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 10/ 4/95. Accepted 12/12/95.




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