Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine.
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.
Belanich
M
M
Applied Genetics Inc., Freeport, New York 11520, USA.
Pastor
M
M
Randall
T
T
Guerra
D
D
Kibitel
J
J
Alas
L
L
Li
B
B
Citron
M
M
Wasserman
P
P
White
A
A
Eyre
H
H
Jaeckle
K
K
Schulman
S
S
Rector
D
D
Prados
M
M
Coons
S
S
Shapiro
W
W
Yarosh
D
D
D000911:Antibodies, Monoclonal; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D002330:Carmustine / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004260:DNA Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008780:Methyltransferases / Q000032:analysis*; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018906:Antineoplastic Agents, Alkylating; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine