Assessment of folate receptor expression and folate uptake in multicentric lymphomas in dogs

Am J Vet Res. 2014 Feb;75(2):187-94. doi: 10.2460/ajvr.75.2.187.

Abstract

Objective: To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs.

Sample: 10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma.

Procedures: Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis.

Results: FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild.

Conclusions and clinical relevance: This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Dog Diseases / diagnostic imaging
  • Dog Diseases / drug therapy
  • Dog Diseases / metabolism*
  • Dogs
  • Female
  • Folic Acid / analogs & derivatives
  • Folic Acid / metabolism*
  • Folic Acid / therapeutic use
  • Folic Acid Transporters / genetics
  • Folic Acid Transporters / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology
  • Lymphoma, Large B-Cell, Diffuse / diagnostic imaging
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / veterinary*
  • Lymphoma, T-Cell, Peripheral / diagnostic imaging
  • Lymphoma, T-Cell, Peripheral / drug therapy
  • Lymphoma, T-Cell, Peripheral / metabolism
  • Lymphoma, T-Cell, Peripheral / veterinary*
  • Male
  • Organotechnetium Compounds / metabolism
  • Organotechnetium Compounds / pharmacology
  • Radionuclide Imaging
  • Vinblastine / analogs & derivatives
  • Vinblastine / therapeutic use

Substances

  • Antineoplastic Agents
  • EC0905
  • Folic Acid Transporters
  • Organotechnetium Compounds
  • Vinblastine
  • Folic Acid