Detection and Prognostic Relevance of Circulating and Disseminated Tumour Cell in Dogs with Metastatic Mammary Carcinoma: A Pilot Study.

Laura Marconato,Riccardo Vidotto,Claudia Zanardello,Antonella Facchinetti,Rita Zamarchi,Erica Melchiotti,Elisabetta Rossi,Marta Vascellari,Katia Capello,Paola Laganga

doi:10.3390/cancers11020163

Abstract

In human breast cancer, both circulating tumour cells (CTCs) in peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are predictive of short survival and may be used as liquid biopsy to guide therapy. Herein we investigate, for the first time, the feasibility to quantify CTCs and DTCs in canine metastatic mammary carcinoma (MMC) with the automated CellSearch platform, which identifies tumour cells by immune-magnetic enrichment and fluorescent labelling. Using this approach before start of treatment, we could detect at least 1 CTC per 7.5 mL of peripheral blood in 12 out of 27 evaluable samples (44.4%) and at least 1 DTC per 1 mL of bone marrow in 11 out of 14 evaluable samples (78.6%). Conversely, we did not find any CTCs in the healthy, negative control dogs (n = 5) that we analysed in parallel. Interestingly, the levels of CTCs/DTCs and the prevalence of positive dogs closely resemble results obtained by CellSearch assay in metastatic breast cancer patients at diagnosis. Moreover, in the canine cohort, the presence of CTCs was significantly associated with poor outcome. These observations identify the first actionable marker in veterinarian oncology to guide treatment of canine MMC. Furthermore, our findings have important implications for human research, since it reinforce the value of canine MMC as model useful to speed up pharmacological studies with primary endpoint of overall survival, given the reduced life-span of the canine species.

Highlights

Animal models have been extensively used in cancer research to investigate biology and genetics of human malignancies, including breast cancer, as well as efficacy and toxicity of chemical and biological agents [1]
Our results demonstrate that mammary carcinoma (MMC) is a systemic disease that involves BM in the great majority of cases, whilst the presence of circulating tumour cells (CTCs) is associated with a worse outcome
When we analysed the expression of M30, a marker of epithelial apoptosis, we found a high level of apoptosis of tumour cells both in peripheral blood (PB) and in BM, to the findings previously reported in newly diagnosed, treatment-naive metastatic solid tumours [36]

Summary

Introduction

Animal models have been extensively used in cancer research to investigate biology and genetics of human malignancies, including breast cancer, as well as efficacy and toxicity of chemical and biological agents [1]. After the recent advent of immunotherapy, much attention has been focused on animal models outbred and with preserved immune system [2]. Cancers 2019, 11, 163 mammary tumours, exhibiting a number of clinical and molecular similarities with human breast cancer [3], canine mammary tumour could be an excellent model to study human disease. Mammary gland carcinomas are a very common malignancy in adult bitches. More than 40% of tumours in female dogs are mammary tumours (MT) [6,8,9] and approximately 30–50% of canine MT are malignant [8,10]

Objectives

Methods

Results

Discussion

Conclusion