title: Assessment of potential doubling time (Tpot), argyrophilic nucleolar organizer regions (AgNOR), and proliferating cell nuclear antigen (PCNA) as predictors of therapy response in canine non-Hodgkin's lymphoma.
abstract: The predictive potential of several proliferation indices for therapeutic outcome was investigated in 55 dogs with spontaneously occurring non-Hodgkin's lymphoma (NHL). Indices included potential doubling time (Tpot), argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). All tumors were of intermediate- or high-grade histology as assessed by the Working Formulation, and all dogs presented with disease of advanced clinical stage. All tumors were treated with an identical chemotherapeutic protocol. Tpot determination by a bromodeoxyuridine (BrdU) delayed-biopsy technique was readily applied in the dog. AgNOR frequency and PCNA-LI were easily obtained from archival, formalin-fixed, paraffin-embedded canine tissues. When accounting for all other prognostic variables by employing multivariate analysis, Tpot (p=0.017), and AgNOR frequency (p=0.021), but not PCNA-LI, were predictive of first remission duration. AgNOR frequency (p=0.033) was also predictive of survival time, and the predictive potential of Tpot approached significance (p=0.076). We conclude that Tpot and AgNOR frequency can be used as predictors of outcome in dogs with NHL, and spontaneous NHL in the dog may have significant potential as a model for further characterization of the association between tumor cell kinetics and chemoresponsiveness.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
authors.forename: W C
authors.initials: WC
authors.lastname: Kisseberth
authors.forename: J E
authors.initials: JE
authors.lastname: Obradovich
authors.forename: F M
authors.initials: FM
authors.lastname: Moore
authors.forename: C A
authors.initials: CA
authors.lastname: London
authors.forename: E G
authors.initials: EG
authors.lastname: MacEwen
authors.forename: M A
authors.initials: MA
authors.lastname: Ritter
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division; D002699:Chlorambucil / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004283:Dog Diseases / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000662:veterinary*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D009697:Nucleolus Organizer Region / Q000648:ultrastructure*; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D012074:Remission Induction; D016622:Silver Staining; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000951:Antigens, Neoplasm; D018809:Proliferating Cell Nuclear Antigen; D002699:Chlorambucil; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate