Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples.
Gynecol Oncol
; 93(1): 98-106, 2004 Apr.
Article
em En
| MEDLINE
| ID: mdl-15047220
ABSTRACT
OBJECTIVES:
The role of MDR1 in clinical paclitaxel resistance remains poorly characterized. This study sought to identify the incidence and significance of P-glycoprotein (P-gp) over-expression on survival, tumor response to paclitaxel and the effect of prior cytotoxic exposure on P-gp expression in patients with paired primary and recurrent ovarian cancer samples.METHODS:
Retrospective survival analysis. P-gp expression was evaluated immunohistochemically with antibodies c494 and c219.RESULTS:
Thirty-two patients were identified from the tumor registry. Median interval between primary and secondary surgery was 17.9 (5.7-40.9) months. Only five primary tumors (16%) demonstrated +++ staining for P-gp. First-line treatment contained paclitaxel in 17 patients (53%) and 26 patients (81%) had been exposed to P-gp exportable chemotherapy before second surgery. Only seven of the recurrent tumors (22%) were +++. Only one of seven (14% (95% CI 0-46%)) recurrent tumors with ++ or +++ staining responded to subsequent paclitaxel, while 8 of 10 (80% (CI 46-100%)) recurrent tumors with 0/+ staining responded (P = 0.025). In multivariate analysis of outcome following second surgery, response to paclitaxel (P = 0.004) and P-gp over-expression (P < 0.001) were significant predictors of survival.CONCLUSIONS:
De novo strong P-gp over-expression is uncommon, appears to change little over time or with prior exposure to chemotherapy. However, P-gp over-expression is a significant prognostic factor, and at the time of disease, relapse is inversely correlated with tumor response to paclitaxel.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Paclitaxel
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Recidiva Local de Neoplasia
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Antineoplásicos Fitogênicos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article