Circulating tumor cells as indicators of metastatic spread of canine mammary tumors

CTC and their clinical and prognostic relevance not only in breast but also in several other types of cancer have been broadly studied in human oncology in the past years. However this research field remains unknown in veterinary oncology. Based on the promising findings in BC research and the recognition of CTC detection as a powerful tool in the determination of risk, prognosis and response to treatment it seems possible that CTC detection might also reveal the same clinical usefulness and therefore this project was based in the following two major hypotheses. First Hypothesis Tumor cells are shed in dog patients baring malignant mammary gland tumors either from the primary tumors or its metastases into to the blood stream directly or indirectly via lymphatic circulation. Similarly to human breast CTC, canine mammary gland CTC occur at very low numbers but despite their rarity they should be detectable through highly sensitive nucleic-acid based methods such as RT-PCR using appropriate mRNA markers. Second Hypothesis The detection of CTC mRNA markers correlates with the histological evidence of vascular invasion by tumor cells in the vicinity of the primary tumor. CTC detection in dogs may also provide important and relevant clinical information in terms of prognosis. Based on these conducting premises the aims of our project were the following: First Objective The identification of sensitive and specific mRNA for the detection of canine MT CTC following three different approaches: First, by evaluation of the mRNA expression of genes with high expression in CMT, second genes which are CTC markers for the detection of human breast cancer CTC, and third by genes which can be identified by comparison of the transcriptome of CMT with the transcriptome of peripheral blood leukocytes. Second Objective The presence of canine CTC markers in the peripheral blood correlates with the histological evidence of vascular invasion in the primary tumor.