Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates

Abstract

BackgroundThe immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas.MethodsFifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry.ResultsData analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4+ (≥ 66.7%) or CD8+ T-cells (<33.3%) were not associated with worse survival rate. Multivariate analysis demonstrated that only lymphocytic infiltrate intensity ≥ 600 (P = 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P < 0.05). The relative percentage of CD4+ T-cells was significantly greater in metastasized tumors (both MC-BMT and MC), (P < 0.05) while the proportion of CD8+ T-cells was higher in MC-BMT without metastasis. Consequently, the CD4+/CD8+ ratio was significantly increased in both groups with metastasis. Regardless of the tumor type, the animals with high proportions of CD4+ and low CD8+ T-cells had decreased survival rates.ConclusionThe intensity of lymphocytic infiltrate and probably the relative abundance of the CD4+ and CD8+ T-lymphocytes may represent important survival prognostic biomarkers for canine mammary carcinomas.

Caracterização clínica, diagnóstico histopatológico e distribuição geográfica das neoplasias mamárias em cadelas de Salvador, Bahia

“…Diversos autores consideram o tamanho tumoral e o estadiamento clínico os parâmetros prognósticos mais importantes (Peleteiro, 1994;Misdorp et al 1999;Cavalcanti & Cassali, 2006;Estrela-Lima et al, 2010;Cassali et al, 2011). Tumores menores que três centíme-tros sem invasão linfática apresentam melhor prognósti-co, quando comparados com aqueles maiores ou que já apresentam metástase para linfonodos (Queiroga & Lopes, 2002;Ferreira et al, 2009).…”

“…A maioria dos tumores apresentava integridade cutânea; entretanto cabe ressaltar que, neste estudo, 100% (33/132) dos tumores que apresentavam ulcerações eram malignos. Sabe-se que os tumores de crescimento rápido, aderentes, com grandes áre-as de necrose, ulcerados ou com acometimento de planos cutâneos adjacentes estão associados a pior prognóstico e menor tempo de sobrevida (Peleteiro, 1994;Cassali, 2002;Estrela-Lima, 2010).…”

“…Também em Medicina Veterinária, tem despertado grande interesse, principalmente pela elevada prevalência de tumores malignos em cadelas, em grande parte reflexo do diagnóstico tardio, que compromete o tratamento e reduz a taxa de sobrevida dos animais (Silva et al, 2004;Cavalcanti & Cassali, 2006;Andrade et al, 2010;Estrela-Lima, 2010).…”

“…Os tumores maiores do que cinco centímetros, de rápido crescimento, aderentes, com grandes áreas de ulceração e com metástase para linfonodos estão associados ao pior prognóstico (Cavalcanti & Cassali, 2006;Ferreira et al, 2009;Estrela-Lima, 2010).…”

CD4+, CD8+, FoxP3+ and HSP60+ Expressions in Cellular Infiltrate of Canine Mammary Carcinoma in Mixed Tumor

“…The role of leukocytes in the tumor microenvironment is not yet fully understood, and several efforts have been made to understand the role of these cells in tumor development. Studies have shown that the lymphocytes presence in mammary mixed tumor (MMT) may be involved in a better or worse prognosis for the patient [1,10].…”