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

被引:18
作者
Marconato, Laura [1 ]
Facchinetti, Antonella [2 ,3 ]
Zanardello, Claudia [4 ]
Rossi, Elisabetta [2 ,3 ]
Vidotto, Riccardo [2 ]
Capello, Katia [4 ]
Melchiotti, Erica [4 ]
Laganga, Paola [1 ]
Zamarchi, Rita [2 ]
Vascellari, Marta [4 ]
机构
[1] Ctr Oncol Vet, I-40037 Sasso Marconi, BO, Italy
[2] Veneto Inst Oncol IOV IRCCS, Padua, Italy
[3] Univ Padua, Dept Surg Oncol & Gastrenterol, I-35128 Padua, Italy
[4] Ist Zooprofilatt Sperimentale Venezie, I-35020 Legnaro, PD, Italy
关键词
circulating tumour cells (CTCs); disseminated tumour cells (DTCs); animal model; metastatic breast cancer; BREAST-CANCER PATIENTS; PERIPHERAL-BLOOD; BONE-MARROW; EPITHELIAL NEOPLASMS; INCIDENCE RATES; POOLED ANALYSIS; POPULATION; CLASSIFICATION; IDENTIFICATION; PROGRESSION;
D O I
10.3390/cancers11020163
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:14
相关论文
共 54 条
[1]   Canine mammary tumors as a model for human disease (Review) [J].
Abdelmegeed, Somaia M. ;
Mohammed, Sulma .
ONCOLOGY LETTERS, 2018, 15 (06) :8195-8205
[2]   Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases [J].
Allard, WJ ;
Matera, J ;
Miller, MC ;
Repollet, M ;
Connelly, MC ;
Rao, C ;
Tibbe, AGJ ;
Uhr, JW ;
Terstappen, LWMM .
CLINICAL CANCER RESEARCH, 2004, 10 (20) :6897-6904
[3]   Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay [J].
Baccelli, Irene ;
Schneeweiss, Andreas ;
Riethdorf, Sabine ;
Stenzinger, Albrecht ;
Schillert, Anja ;
Vogel, Vanessa ;
Klein, Corinna ;
Saini, Massimo ;
Baeuerle, Tobias ;
Wallwiener, Markus ;
Holland-Letz, Tim ;
Hoefner, Thomas ;
Sprick, Martin ;
Scharpff, Martina ;
Marme, Frederik ;
Sinn, Hans Peter ;
Pantel, Klaus ;
Weichert, Wilko ;
Trumpp, Andreas .
NATURE BIOTECHNOLOGY, 2013, 31 (06) :539-U143
[4]   The effect of neutering on the risk of mammary tumours in dogs - a systematic review [J].
Beauvais, W. ;
Cardwell, J. M. ;
Brodbelt, D. C. .
JOURNAL OF SMALL ANIMAL PRACTICE, 2012, 53 (06) :314-322
[5]   Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles [J].
Benjamin, SA ;
Lee, AC ;
Saunders, WJ .
VETERINARY PATHOLOGY, 1999, 36 (05) :423-436
[6]   Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data [J].
Bidard, Francois-Clement ;
Peeters, Dieter J. ;
Fehm, Tanja ;
Nole, Franco ;
Gisbert-Criado, Rafael ;
Mavroudis, Dimitrios ;
Grisanti, Salvatore ;
Generali, Daniele ;
Garcia-Saenz, Jose A. ;
Stebbing, Justin ;
Caldas, Carlos ;
Gazzaniga, Paola ;
Manso, Luis ;
Zamarchi, Rita ;
Fernandez de Lascoiti, Angela ;
De Mattos-Arruda, Leticia ;
Ignatiadis, Michail ;
Lebofsky, Ronald ;
van Laere, Steven J. ;
Meier-Stiegen, Franziska ;
Sandri, Maria-Teresa ;
Vidal-Martinez, Jose ;
Politaki, Eleni ;
Consoli, Francesca ;
Bottini, Alberto ;
Diaz-Rubio, Eduardo ;
Krell, Jonathan ;
Dawson, Sarah-Jane ;
Raimondi, Cristina ;
Rutten, Annemie ;
Janni, Wolfgang ;
Munzone, Elisabetta ;
Caranana, Vicente ;
Agelaki, Sofi A. ;
Almici, Camillo ;
Dirix, Luc ;
Solomayer, Erich-Franz ;
Zorzino, Laura ;
Johannes, Helene ;
Reis-Filho, Jorge S. ;
Pantel, Klaus ;
Pierga, Jean-Yves ;
Michiels, Stefan .
LANCET ONCOLOGY, 2014, 15 (04) :406-414
[7]   A pooled analysis of bone marrow micrometastasis in breast cancer [J].
Braun, S ;
Vogl, FD ;
Naume, B ;
Janni, W ;
Osborne, MP ;
Coombes, RC ;
Schlimok, G ;
Diel, IJ ;
Gerber, B ;
Gebauer, G ;
Pierga, JY ;
Marth, C ;
Oruzio, D ;
Wiedswang, G ;
Solomayer, EF ;
Kundt, G ;
Strobl, B ;
Fehm, T ;
Wong, GYC ;
Bliss, J ;
Vincent-Salomon, A ;
Pantel, K .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (08) :793-802
[8]   The application of circulating tumor cells detecting methods in veterinary oncology [J].
Chmielewska, M. ;
Losiewicz, K. ;
Socha, P. ;
Mecik-Kronenberg, T. ;
Wasowicz, K. .
POLISH JOURNAL OF VETERINARY SCIENCES, 2013, 16 (01) :141-151
[9]   Circulating tumor cells, disease progression, and survival in metastatic breast cancer [J].
Cristofanilli, M ;
Budd, GT ;
Ellis, MJ ;
Stopeck, A ;
Matera, J ;
Miller, MC ;
Reuben, JM ;
Doyle, GV ;
Allard, WJ ;
Terstappen, LWMM ;
Hayes, DF .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (08) :781-791
[10]   Multiple RT-PCR markers for the detection of circulating tumour cells of metastatic canine mammary tumours [J].
da Costa, A. ;
Kohn, B. ;
Gruber, A. D. ;
Klopfleisch, R. .
VETERINARY JOURNAL, 2013, 196 (01) :34-39