P-glycoprotein as a prognostic indicator in pre- and postchemotherapy ovarian adenocarcinoma

Mahmoud A. Khalifa, Ahmed A. Abdoh, Robert S. Mannel, Joan L. Walker, Lee H. Angros, Kyung Whan Min

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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 Cage, surgical stage, and presence of residual tumor) and included occurrence of postchemotherapy tumors and P-gp positivity in postchemotherapy neoplasms as time-dependant 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.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalInternational Journal of Gynecological Pathology
Volume16
Issue number1
DOIs
StatePublished - Jan 1997

Keywords

  • Adenocarcinoma
  • Drug resistance
  • Gene expression
  • Ovarian neoplasms
  • P-glycoprotein
  • Recurrent tumors

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