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Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples
- Source :
- Gynecologic oncology. 93(1)
- Publication Year :
- 2003
-
Abstract
- Objective . 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 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.
- Subjects :
- Adult
medicine.medical_specialty
Pathology
Paclitaxel
medicine.medical_treatment
Gastroenterology
chemistry.chemical_compound
Internal medicine
Medicine
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
Survival rate
Survival analysis
Aged
Retrospective Studies
Ovarian Neoplasms
Chemotherapy
Taxane
business.industry
Obstetrics and Gynecology
Retrospective cohort study
Middle Aged
medicine.disease
Antineoplastic Agents, Phytogenic
Immunohistochemistry
Survival Rate
Oncology
chemistry
Female
Neoplasm Recurrence, Local
business
Ovarian cancer
Subjects
Details
- ISSN :
- 00908258
- Volume :
- 93
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Gynecologic oncology
- Accession number :
- edsair.doi.dedup.....6ecf7d0abaeca36eac20c2cb61384647