title: Expression of Apoptosis-regulating Proteins Bcl-2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma.
abstract: BACKGROUND
  Dysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs.
  
  
  OBJECTIVE
  That Bcl-2/Bax expression patterns differ between lymphoma immunophenotypes, and that Bcl-2/Bax ratio is correlated with prognosis.
  
  
  METHODS
  Fifty-five client-owned dogs with multicentric lymphoma and 5 healthy dogs.
  
  
  METHODS
  Prospective, case-control study. We compared 3 methods (flow cytometry, qRT-PCR, Western blot) for Bcl-2 and Bax quantification in a subset of dogs. The effect of time on Bcl-2/Bax ratios measured by flow cytometry was assessed in lymphoma cell lines. Immunophenotype and Bcl-2/Bax expression by flow cytometry were determined in LN aspirates from all dogs with multicentric lymphoma compared to healthy dogs. Progression-free survival (PFS) was retrospectively evaluated in a group of dogs all receiving similar treatment.
  
  
  RESULTS
  Bcl-2/Bax ratios remain consistent for at least 5 days after sample collection. Bcl-2/Bax ratio was higher in dogs with T-cell lymphoma (TCL; median 0.97, range 0.37-1.36) compared to B-cell lymphoma (BCL; median 0.36, range 0.07-1.45) (P < .0001) and normal dogs (median 0.36, range 0.21-0.48) (P = .0006), respectively. Dogs with Bcl-2/Bax ratios higher than the median of the group experienced a median PFS of 101 days and dogs with ratios equal and lower than the median had PFS of 130 days (P = .19).
  
  
  CONCLUSIONS
  Higher intrinsic resistance to apoptosis following cytotoxic treatment might contribute to the less favorable prognosis associated with multicentric TCL in dogs. Whether Bcl-2/Bax will be helpful to identify canine BCL and TCL with more aggressive and more indolent behavior, respectively, should be evaluated in larger prospective clinical studies.
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
authors.forename: K
authors.initials: K
authors.lastname: Meichner
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
authors.forename: J E
authors.initials: JE
authors.lastname: Fogle
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
authors.forename: L
authors.initials: L
authors.lastname: English
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.|Lineberger Comprehensive Cancer Center, Chapel Hill, NC.|Comparative Medicine Institute, North Carolina State University, Raleigh, NC.
authors.forename: S E
authors.initials: SE
authors.lastname: Suter
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis; D016022:Case-Control Studies; D004283:Dog Diseases / Q000188:drug therapy / Q000473:pathology*; D004285:Dogs; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D015972:Gene Expression Regulation, Neoplastic; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D008297:Male; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D013599:Systole; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
keywords: Canine; Flow cytometry; Lymphosarcoma; Programmed cell death