Circulating Tumour Cells and Their Association with Bone Metastases in Patients with Neuroendocrine Tumours

Overview

Journal Br J Cancer

Specialty Oncology

Date 2019 Jan 15

PMID 30636773

Citations 16

Authors

Francesca M Rizzo

Clare Vesely

Alexa Childs

Teresa Marafioti

Mohid S Khan

Dalvinder Mandair

Mauro Cives

Leah Ensell

Helen Lowe

Ayse U Akarca

TuVinh Luong

Martyn Caplin

Christos Toumpanakis

Daniel Krell

Christina Thirlwell

Franco Silvestris

John A Hartley

Tim Meyer

Affiliations

Soon will be listed here.

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.

Citing Articles

Stem cell-like circulating tumor cells identified by Pep@MNP and their clinical significance in pancreatic cancer metastasis.

Chu X, Zhong X, Zang S, Wang M, Li P, Ma Y Front Oncol. 2024; 14:1327280.

PMID: 38983932 PMC: 11231205. DOI: 10.3389/fonc.2024.1327280.

Circulating Tumour Cells in the Prediction of Bone Metastasis.

Choi S, Sun A, Cheung J, Ho J Cancers (Basel). 2024; 16(2).

PMID: 38254743 PMC: 10813668. DOI: 10.3390/cancers16020252.

Role of Selected Circulating Tumor Biomarkers in Patients with Skeletal Metastatic Pancreatic Neuroendocrine Neoplasms.

Rosiek V, Janas K, Witkowska M, Kos-Kudla B J Clin Med. 2023; 12(14).

PMID: 37510802 PMC: 10380808. DOI: 10.3390/jcm12144687.

Circulating biomarkers for diagnosis and therapeutic monitoring in bone metastasis.

Song M, Park S, Cho S J Bone Miner Metab. 2023; 41(3):337-344.

PMID: 36729305 DOI: 10.1007/s00774-022-01396-6.

Risk Stratification of Pancreatic Neuroendocrine Neoplasms Based on Clinical, Pathological, and Molecular Characteristics.

Choi J, Paik W J Clin Med. 2022; 11(24).

PMID: 36556070 PMC: 9786745. DOI: 10.3390/jcm11247456.

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