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Mammary tumors are among the most common neoplastic processes in female dogs. Prostaglandin E2, the catalytic product of Cox-2, may promote tumor development and angiogenesis. It has been investigated in several human cancers and also correlated with the evolution of the disease. However, the clinical implications of tumor pathology require more investigation in veterinary medicine. Angiogenesis is essential for the growth and metastasis of major solid tumors and has been correlated with prognosis in human and canine breast cancer. The aim of this study was to evaluate Cox-2 expression and microvessel density in canine mammary carcinomas and to correlate them with overall survival of the animal. Cox-2 and angiogenesis were assessed by immunohistochemistry in 46 mammary carcinomas (19 ductal and 27 metaplastic) and in healthy mammary glands. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD31 staining. Immunostaining revealed that 46/46 (100%) of the tumors were positive for Cox-2 and CD31, and there was no statistical difference among tumor types. Cox-2 protein expression correlated positively with CD31 staining ( r = 0.3742, P = .0104) but did not correlate significantly with tumor type. Longer overall survival was observed in metaplastic carcinomas ( P = .028), in tumors with low microvessel density ( P = .0002) and with low Cox-2 score ( P = .01). Our results demonstrate that increased microvessel density and increased Cox-2 expression were linearly related in the canine mammary tumors studied and were also related to worse prognosis and shorter overall survival. This suggests that Cox-2 inhibitors could be an alternative for the treatment and control of advanced neoplastic mammary disease in female dogs.

The immunohistochemical expression of p63, DeltaNp63, and p53 was studied in mixed tumors of canine mammary glands (13 benign mixed tumors and 19 carcinomas arising from benign mixed tumors) to determine the role of p63 and its isoform DeltaNp63 in the development of mixed tumors, as well as to assess its relation with p53. P63 was expressed in myoepithelial cells of all benign mixed tumors and in 18 of 19 carcinomas in mixed tumors. The p63-negative carcinoma in mixed tumors was invasive, and a loss of p63 was detected in the other malignant tumors showing a discontinuous p63-stained myoepithelial layer. DeltaNp63 was expressed in all benign mixed tumors but only in p63-positive carcinomas in mixed tumors. Despite its positive correlation with p63 expression in carcinomas in mixed tumors (r = 0.8323, P < .00001), DeltaNp63 expression showed a decrease in benign tumors. Positivity for p53 was detected in 2 of 13 and 1 of 19 benign mixed tumors and carcinomas in mixed tumors, respectively. There was no correlation between p63 or DeltaNp63 and p53 expression. Our data support the notion that the decrease of p63 expression, in particular of its isoform DeltaNp63, seems to be an important factor in the development of carcinomas in mixed tumors.