title: Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples.
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 < 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.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Skates
authors.forename: Tina
authors.initials: T
authors.lastname: Glyptis
authors.forename: Arlan F
authors.initials: AF
authors.lastname: Fuller
authors.forename: Annekathryn
authors.initials: A
authors.lastname: Goodman
authors.forename: Michael V
authors.initials: MV
authors.lastname: Seiden
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D017239:Paclitaxel / Q000627:therapeutic use*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel