P-glycoprotein expression in canine lymphoma: a relevant, intermediate model of multidrug resistance

Cancer. 1996 May 1;77(9):1892-8. doi: 10.1002/(SICI)1097-0142(19960501)77:9<1892::AID-CNCR20>3.0.CO;2-U.

Abstract

Background: Despite extensive investigation, the role of MDR of human cancer remains unclear. Canine lymphoma is a spontaneously arising correlate of human non-Hodgkin's lymphoma that may complement other in vivo models for investigation of issues related to MDR.

Methods: Immunoreactivity of primary antibodies to the human MDR1 gene product, p-glycoprotein 170 (Pgp), were determined in both a retrospective (n=76) and prospective (n=15) survey of canine lymphoma. Known prognostic factors and response to chemotherapy were correlated with categorical designations of Pgp expression.

Results: When combined, 61 of 91 samples (67%) were negative for Pgp, 16 of 91 (17.5%) had strong Pgp immunoreactivity in >50% of the malignant population and 14 of 91 (15.5%) had Pgp reactivity in 10-50% of cells. Pgp expression was greater after relapse compared with pretreatment samples [C494 83% vs. 25%; P=0.012 and C219 73% vs. 27%; P=0.04]. Pretreatment Pgp expression was an independent negative predictor of overall survival (median=225d vs. 367d; P=0.02).

Conclusions: Pgp expression in spontaneous canine lymphoma is similar to that reported in human non-Hodgkin's lymphoma. Use of this model may expedite investigation of novel strategies for MDR prevention or modulation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Animals
  • Antibodies, Monoclonal
  • Disease Models, Animal
  • Dog Diseases / drug therapy
  • Dog Diseases / genetics*
  • Dog Diseases / pathology
  • Dogs
  • Drug Resistance, Neoplasm / genetics
  • Forecasting
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymph Nodes / pathology
  • Lymphoma / drug therapy
  • Lymphoma / genetics*
  • Lymphoma / pathology
  • Lymphoma / veterinary*
  • Lymphoma, Non-Hodgkin / genetics
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Phenotype
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies, Monoclonal