P-glycoprotein expression in canine lymphoma: a relevant, intermediate model of multidrug resistance.
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.
Lee
J J
JJ
Department of Anatomy, Physiological Sciences, and RAdiology, North Carolina State University, College of Veterinary Medicine, Raleigh, 27606, USA.
Hughes
C S
CS
Fine
R L
RL
Page
R L
RL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000662:veterinary*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal