Identification of prognostic factors in canine mammary malignant tumours: a multivariable survival study

Eighty-five female dogs affected by spontaneous malignant mammary neoplasias were followed up for a 2-year post-operative period. In univariate analysis, tumour characteristics such as size, mode of growth, regional lymph node metastases, tumour cell MIB-1 LI and MMP-9 and uPA expressions in tumour-adjacent fibroblasts, were associated with both survival and disease-free intervals. Histological type and grade were related with overall survival while VEGF and TIMP-2 were not significantly associated with none of the outcome parameters. In multivariable analysis, only a MIB-1 labelling index higher than 40% and a stromal expression of MMP-9 higher than 50% retained significant relationships with poor overall and disease-free survival.The results of this study indicate that MMP-9 and Ki-67 are independent prognostic markers of canine malignant mammary tumours. Furthermore, the high stromal expressions of uPA and MMP-9 in aggressive tumours suggest that these molecules are potential therapeutic targets in the post-operative treatment of canine mammary cancer.Mammary tumours are the most prevalent neoplasms in intact female dogs [1] and it has been described that approximately 40 to 50% are histologically malignant [2]. Mammary cancers have, however, variable biological behaviours, hampering estimates of individual clinical outcomes based solely on their histological and clinical characteristics [3].Several studies reported that factors such as tumour size [4,5], histological type [6], histological grade [7,8], mode of growth [4,9] and lymph node status [10,11] influence the prognosis of canine malignant mammary tumours (MMTs) and these factors are currently used in practice to establish a prognosis. These clinical and histological factors are, however, crude determinants and are not used, in routine practice, as indicators of the need for adjuvant post-operative therapies.In human breast cancer, molecular markers (oestrogen and progesterone receptors and c-erbB2) are ro