Computer-assisted image analysis of intratumoral vessel density in mammary tumors from dogs

Objective - To determine whether intratumoral microvessel density can be used to distinguish benign from malignant mammary tumors in dogs and to predict the outcome of surgical treatment for small volume (< 3-cm diameter) tumors. Sample Population - Tissue sections from 58 mammary tumors (42 malignant and 16 benign) from dogs. Procedure - Mammary tumors were stained by immunohistochemistry for factor VIII-related antigen. Computer-assisted image analysis was used to determine intratumoral vessel density in immunostained areas. Total vascular density (TVD), calculated from 3 non-overlapping fields, was analyzed for correlation with patient or tumor histomorphologic characteristics, and results obtained by surgical treatment of small volume tumors. Results - Mean TVD of malignant tumors was significantly greater than that of benign tumors. Total vascular density was not correlated with patient age, sex, reproductive status, clinical tumor stage, or histologic type. For small volume (< 3-cm diameter) malignant tumors, mean TVD was higher in tumors that recurred after surgery than in tumors that did not recur; however, TVD was not predictive of time to recurrence. Conclusion and Clinical Implications - Immunohistochemistry and computer-assisted image analysis allowed objective quantitation of intratumoral microvessel density in formalin-fixed, paraffin-embedded tissue sections. Tumors with high TVD were more likely to recur after surgical treatment than tumors with low TVD suggesting that TVD measurements can be used by the clinician, in addition to histologic type and clinical stage, to predict prognosis after surgical treatment. These data also provide rationale for use of antiangiogenesis strategies for treatment of malignant mammary tumors in dogs.