Expressão do fator de crescimento endotelial vascular em tumores mamários de cadelas

Background: Breast cancer is the most common cause of cancer-related death in canine female. Vascular endothelial growth factor is a major inducer of angiogenesis and has marked expression in mammary tumoral cells. The role of vascular endothelial growth factor that assumed to be most potent angiogenesis factor is ambiguous in breast cancer. Studies suggest that VEGF expression is higher in malignant than in benign tumors, and its correlation with invasion and growth of canine mammary tumors and unfavorable outcomes. The aim of this study was to determine and compare the immunohistochemical expression of VEGF in malignant and benign mammary tumors in bitches. Materials, Methods & Results: Fifty five malignant tumors were analyzed and sixteen benign tumors of dogs using a polyclonal antibody to determine the expression of VEGF by a semi-quantitative method (based on the sum of the ratio and intensity of color of the tumor cells) and a quantitative (performed by means of a computerized image capture and analysis). The marker VEGF positivity was determined by the presence of at least one tumor cell with brown cytoplasmic staining clear and unambiguous. The VEGF expression was compared between each histopathological group by Microsoft Office Excel 2007 and PHStat2 statistical software, version 2.0. We used the chi-squared test (χ2 ), to detect differences in the expression score in methods between the variable histopathology type and Student’s t-test for comparisons between the optical density means. The confidence interval was set at 95% and P values < 0.05 were considered significant. Strong immunostaining was found in 33 (58.9%) malignant tumors and in 11 (78.6%) benign and weak immunostaining in 23 (41.1%) malignant and three (21.4%) benign. The optical density of malignant mammary tumors was 113.5 (± 30.9) and benign was 117 (± 31.9). Discussion: In all tumors examined VEGF immunostaining was present diffusely in the cytoplasm of tumor cells and the vascular endothelium, were also observed in the neoplasic cells located closed to necrotic centers, suggesting that VEGF expression is highest in significant tumor necrosis. Strong immunostaining was observed in most malignant tumors, similarly to what was found in other studies, in which malignant mammary tumors were highly positive for VEGF marking, linking them to unfavorable outcomes. However, high VEGF expression found in benign tumors is divergent, and may have been affected by methodological factors or physiological changes that allow the occurrence of angiogenesis during the development of benign neoplasias. Among the malignant tumors was not observed statistical difference between strong and weak immunostaining, as well as between the optical densities, demonstrating that the pathological types studied exhibited the same behavior, differently from what was found by another study in which the pathological types were heterogeneous. Statistical analysis failed to correlate the immunohistochemical expression of VEGF between malignant and benign tumors in bitches and among the different types in relation to malignant histopathological score and the optical density; therefore, it is not possible to establish a criterion of malignancy for these tumors according to immunohistochemical expression of VEGF.