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转移性乳腺癌犬循环肿瘤细胞和播散肿瘤细胞的检测及其预后相关性:一项初步研究

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

作者信息

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

机构信息

Centro Oncologico Veterinario, 40037 Sasso Marconi (BO), Italy.

Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.

出版信息

Cancers (Basel). 2019 Feb 1;11(2):163. 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 ( = 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.

摘要

在人类乳腺癌中,外周血中的循环肿瘤细胞(CTC)和骨髓中的播散肿瘤细胞(DTC)均预示着生存期较短,并且可用作液体活检以指导治疗。在此,我们首次研究了使用自动化CellSearch平台对犬转移性乳腺癌(MMC)中的CTC和DTC进行定量的可行性,该平台通过免疫磁珠富集和荧光标记来识别肿瘤细胞。在治疗开始前使用这种方法,我们在27个可评估样本中的12个(44.4%)中,每7.5 mL外周血中至少检测到1个CTC,在14个可评估样本中的11个(78.6%)中,每1 mL骨髓中至少检测到1个DTC。相反,在我们同时分析的5只健康阴性对照犬中未发现任何CTC。有趣的是,CTC/DTC的水平以及阳性犬的患病率与转移性乳腺癌患者诊断时通过CellSearch检测获得的结果非常相似。此外,在犬类队列中,CTC的存在与不良预后显著相关。这些观察结果确定了兽医肿瘤学中第一个可用于指导犬MMC治疗的可操作标志物。此外,我们的发现对人类研究具有重要意义,因为鉴于犬类寿命较短,这强化了犬MMC作为一种有助于加速以总生存期为主要终点的药理学研究的有用模型的价值。

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