P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma.
METHODS
Multidrug resistance in chemotherapy for cancer is characterized by increased genetic expression of P-glycoprotein, which acts as an ATP-dependent drug-efflux pump. To determine whether P-glycoprotein levels are of prognostic value in such cases, we measured these levels immunohistochemically in a retrospective study of sequential tumor samples from 67 children with neuroblastoma.


RESULTS
P-glycoprotein was not detected in pretreatment samples from either of the 2 patients with Stage I disease, any of the 21 with Stage II disease, or any of the 8 with Stage IVS disease, but it was detected in the samples from 1 of the 17 patients with Stage III disease (6 percent) and 12 of the 19 with Stage IV disease (63 percent). Of the 44 patients with nonlocalized neuroblastoma (Stage III, IVS, or IV), 26 of the 31 who were negative for P-glycoprotein had a complete response to primary treatment, as compared with 6 of the 13 who were positive for P-glycoprotein (84 percent vs. 46 percent, P = 0.0232 by Fisher's exact test). Log-rank analysis of outcome, with simultaneous stratification according to tumor stage and age, showed that the group that was negative for P-glycoprotein had significantly longer relapse-free survival (P = 0.0011) and overall survival (P = 0.0373) than the group that was positive.


CONCLUSIONS
Expression of P-glycoprotein before treatment may predict the success or failure of therapy for nonlocalized neuroblastoma. Neuroblastoma may be a promising tumor to treat with anticancer drug therapy combined with a chemosensitizing agent capable of reversing P-glycoprotein-mediated multidrug resistance.
Chan
H S
HS
Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.
Haddad
G
G
Thorner
P S
PS
DeBoer
G
G
Lin
Y P
YP
Ondrusek
N
N
Yeger
H
H
Ling
V
V
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002648:Child; D004351:Drug Resistance; D016259:Genes, myc; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins