Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours

Rizzo, Francesca M., Vesely, Clare, Childs, Alexa, Marafioti, Teresa, Khan, Mohid S., Mandair, Dalvinder, Cives, Mauro, Ensell, Leah, Lowe, Helen, Akarca, Ayse U., Luong, TuVinh, Caplin, Martyn, Toumpanakis, Christos, Krell, Daniel, Thirlwell, Christina, Silvestris, Franco, Hartley, John A. and Meyer, Tim 2019. Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours. British Journal of Cancer 120 (3) , 294–300. 10.1038/s41416-018-0367-4

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Abstract

Background Bone metastases are associated with a worse outcome in patients with neuroendocrine tumours (NETs). Tumour overexpression of C-X-C chemokine receptor 4 (CXCR4) appears predictive of skeletal involvement. We investigated the role of circulating tumour cells (CTCs) and CXCR4 expression on CTCs as potential predictors of skeleton invasion. Methods Blood from patients with metastatic bronchial, midgut or pancreatic NET (pNET) was analysed by CellSearch. CXCR4 immunohistochemistry was performed on matched formalin-fixed paraffin-embedded (FFPE) samples. Results Two hundred and fifty-four patients were recruited with 121 midgut and 119 pNETs, of which 51 and 36% had detectable CTCs, respectively. Bone metastases were reported in 30% of midgut and 23% of pNET patients and were significantly associated with CTC presence (p = 0.003 and p < 0.0001). In a subgroup of 40 patients, 85% patients with CTCs had CTCs positive for CXCR4 expression. The proportion of CXCR4-positive CTCs in patients with bone metastases was 56% compared to 35% in those without (p = 0.18) it. Staining for CXCR4 on matched FFPE tissue showed a trend towards a correlation with CXCR4 expression on CTCs (p = 0.08). Conclusions CTC presence is associated with bone metastases in NETs. CXCR4 may be involved in CTC osteotropism and present a therapeutic target to reduce skeletal morbidity.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0007-0920
Date of Acceptance:	4 December 2018
Last Modified:	12 Mar 2025 16:00
URI:	https://orca.cardiff.ac.uk/id/eprint/176563

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