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.
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.
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).
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.
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Prof. Tim Meyer is partly funded by UCLH Biomedical Research Centre and the work was supported by the UCL Experimental Cancer Medicine Centre. This research project was supported by ESMO with the aid of a grant from Roche and by University College London Cancer Research UK (UCL CRUK) Development Fund Award No. 163011. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO or Roche.
F.M.R. and T.M. wrote the manuscript. F.M.R., C.V., A.C., F.S., T.M. contributed to study design and conduct. T.M., L.E., H.L., A.U.A., T.L., J.A.H. contributed to the analysis of blood and tissue samples. A.C., M.S.K., D.M., M.C., C.T., D.K., C.T., and T.M. contributed to the recruitment of patients. M.C. analysed the data and provided statistical support. All authors were involved in revising the manuscript critically, approving the final version for submission and agreeing to be accountable for all aspects of the work.