title: Positive Interplay Between CD3+ T-lymphocytes and Concurrent COX-2/EGFR Expression in Canine Malignant Mammary Tumors.
abstract: OBJECTIVE
  The ability of tumors to evade the immune system is one of cancer hallmarks. In breast cancer, it has been demonstrated that the cyclooxygenase-2(+)/ epidermal growth factor receptor(+) (COX-2(+)/EGFR(+)) status might influence tumor microenvironment allowing escape of cancer cells to the immune system. This topic is unknown in canine mammary tumors (CMT). Therefore, the potential relationship between CD3(+) T-lymphocytes and concurrent COX-2/EGFR expression was investigated.
  
  
  METHODS
  Formalin-fixed paraffin-embedded malignant CMT samples (n=63) were submitted to immunohistochemical staining to detect CD3, COX-2 and EGFR.
  
  
  RESULTS
  Tumoral CD3(+) T-lymphocytes were significantly associated with tubular differentiation grade (p=0.006), tumor necrosis (p=0.025), histological grade of malignancy (p=0.027) and presence of lymph node metastasis (p=0.009). A correlation between COX-2 and EGFR was observed (r=0.741, p<0.0001). The COX-2(+)/EGFR(+) group was associated with tumor size (p=0.002), mitotic index (p=0.019), histological grade of malignancy (p=0.035) and presence of lymph node metastasis (p=0.041). CD3(+) T-lymphocytes and COX-2/EGFR groups were significantly associated (p=0.025) and positively correlated (r=0.399; p=0.003).
  
  
  CONCLUSIONS
  The present results suggest that the COX-2(+)/EGFR(+) status may be part of a strategy adopted by tumor cells to evade the cytotoxic tumor-specific immune responses.
authors.affiliation: Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal CECAV, Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Carvalho
authors.affiliation: Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal CECAV, Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pires
authors.affiliation: Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal CECAV, Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal.
authors.forename: Justina
authors.initials: J
authors.lastname: Prada
authors.affiliation: Unidade Academica de Medicina Veterinária, Universidade Federal de Campina Grande, Patos, Rua Sinfrônio Nazaré, 1 Centro, Sousa, PB, Brazil.
authors.forename: Adriano Fernandes
authors.initials: AF
authors.lastname: Ferreira
authors.affiliation: Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal Center for the Study of Animal Sciences, CECA-ICETA, University of Porto, Porto, Portugal Center for Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Quinta dos prados, Vila Real, Portugal fqueirog@utad.pt.
authors.forename: Felisbina L
authors.initials: FL
authors.lastname: Queiroga
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004285:Dogs; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D017252:CD3 Complex; D051546:Cyclooxygenase 2; D066246:ErbB Receptors
keywords: CD3; COX-2; Canine mammary tumors; EGFR