P-glycoprotein as a prognostic indicator in pre- and postchemotherapy ovarian adenocarcinoma.
P-glycoprotein (P-gp) is a plasma membrane efflux transporter that maintains the intracellular concentration of chemotherapeutic agents at low levels. Since the clinical outcome of ovarian adenocarcinoma depends largely on its response to chemotherapy, an objective assessment of P-gp expression could serve as a prognostic indicator. Eighty-five patients were studied. Available tissue sections from the primary tumor (n = 75) and persistent or recurrent lesions (n = 19) were tested with anti-P-gp (JSB-1) monoclonal IgG. Multivariate survival analysis using Cox regression was performed controlling for fixed covariates (age, surgical stage, and presence of residual tumor) and included occurrence of postchemotherapy tumors and P-gp positivity in postchemotherapy neoplasms as time-dependent variables. P-gp was expressed in 49 prechemotherapy (65.3%) and 14 postchemotherapy (73.7%) tumors. After controlling for potentially confounding factors, patients with P-gp-positive postchemotherapy neoplasms were at three times greater risk of dying within 2 years than their counterparts with P-gp-negative tumors (hazard ratio = 3.1: 95% confidence interval = 1.2, 9.1; p < 0.05). Detection of P-gp-expressive subclones can serve as an independent poor prognostic indicator for patients with postchemotherapy tumors.
Khalifa
M A
MA
Department of Pathology, Memorial University of Newfoundland, St. John's, Canada.
Abdoh
A A
AA
Mannel
R S
RS
Walker
J L
JL
Angros
L H
LH
Min
K W
KW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000276:immunology; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D018432:Drug Resistance, Multiple / Q000502:physiology; D004358:Drug Therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D011379:Prognosis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor