title: Understanding of the immunological heterogeneity of canine mammary carcinomas to provide immunophenotypic features of circulating leukocytes as clinically relevant prognostic biomarkers.
abstract: We have evaluated the phenotypic features of peripheral blood leukocytes as putative novel biomarkers with prognostic values to monitor canine mammary carcinomas. Female dogs were categorized into distinct groups, referred as mammary carcinoma in benign mixed tumor-MC-BMT and mammary carcinoma-MC. Our findings demonstrate that decreased percentage of B-cells along with increased frequency of NK-cells, CD8(+)T-cells, and CD8(+)CD5(Low+)T-cells beside higher T/B-cells and lower CD4(+)/CD8(+) ratio were the hallmarks of MC-BMT. Despite the lower expression of MHCI and MHCII, the lymphocytes from MC-BMT and MC displayed higher migration potential as suggested by enhanced frequency of CD18(+) events. Although increased levels of macrophage-like cells/(CD14(+)CD16(+)) and decreased levels of MHCII expression were a common phenotypic feature in mammary carcinoma, down-regulation of MHCI was selectively observed in MC. Decreased frequency of CD4(+) T-cells with increased levels of CD8(+) T-cells and lower CD4(+)/CD8(+) T-cell ratio were relevant biomarkers of MC-BTM(-). Although decreased expression of MHCI by monocytes was observed in MC-BTM regardless of the presence of lymph node metastasis, this phenotypic feature was restricted to MC free of metastasis. The CD4(+)/CD8(+) T-cells ratio lower than 1.8 was elected as a valid parameter with outstanding performance to predict survival in MC-BMT. On the other hand, the MHCI expression by monocytes higher than 10(2) MFI showed good value to estimate worse outcome in MC. These results should help to improve our understanding of the immunological heterogeneity of canine mammary carcinomas and provide tools for the determination of cut-off scores of clinically relevant immonophenotypic prognostic biomarkers.
authors: Laboratório de Patologia Comparada, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil, Caixa Postal 486, Belo Horizonte, MG, 31270-901, Brazil.
authors: Alessandra
authors: A
authors: Estrela-Lima
authors: Márcio Sobreira Silva
authors: MS
authors: Araújo
authors: João Moreira
authors: JM
authors: da Costa-Neto
authors: Lorena Gabriela Rocha
authors: LG
authors: Ribeiro
authors: Karine Araújo
authors: KA
authors: Damasceno
authors: Mário Jorge Melhor Heine
authors: MJ
authors: D'Assis
authors: Olindo Assis
authors: OA
authors: Martins-Filho
authors: Andréa
authors: A
authors: Teixeira-Carvalho
authors: Rogéria
authors: R
authors: Serakides
authors: Geovanni Dantas
authors: GD
authors: Cassali
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004285:Dogs; D005260:Female; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D007964:Leukocytosis; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009504:Neutrophils / Q000276:immunology; D011379:Prognosis; D012016:Reference Values; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor