Assessment of folate receptor expression and folate uptake in multicentric lymphomas in dogs.
OBJECTIVE
To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs.


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


METHODS
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
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.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
Michael O
MO
Childress
Deepika
D
Dhawan
Christopher P
CP
Leamon
Margaret A
MA
Miller
José A
JA
Ramos-Vara
James F
JF
Naughton
Philip S
PS
Low
Deborah W
DW
Knapp
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004283:Dog Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005492:Folic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D058972:Folic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D016411:Lymphoma, T-Cell, Peripheral / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D015609:Organotechnetium Compounds / Q000378:metabolism / Q000494:pharmacology; D011877:Radionuclide Imaging; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000970:Antineoplastic Agents; C579135:EC0905; D058972:Folic Acid Transporters; D015609:Organotechnetium Compounds; D014747:Vinblastine; D005492:Folic Acid