Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples.

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.

• Authors: Richard T Penson, Esther Oliva, Steven J Skates, Tina Glyptis, Arlan F Fuller Jr, Annekathryn Goodman, Michael V Seiden
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 93 Issue 1 Pg. 98-106 (Apr 2004) ISSN: 0090-8258 [Print] United States
• PMID: 15047220 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• Paclitaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, metabolism)
• Adult
• Aged
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, metabolism)
• Ovarian Neoplasms (drug therapy, metabolism, surgery)
• Paclitaxel (therapeutic use)
• Retrospective Studies
• Survival Rate