Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture

(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour...

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Main Authors: Aaron B. Beasley, Timothy W. Isaacs, Tersia Vermeulen, James Freeman, Jean-Louis DeSousa, Riyaz Bhikoo, Doireann Hennessy, Anna Reid, Fred K. Chen, Jacqueline Bentel, Daniel McKay, R. Max Conway, Michelle R. Pereira, Bob Mirzai, Leslie Calapre, Wendy N. Erber, Melanie R. Ziman, Elin S. Gray
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/23/5990
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author Aaron B. Beasley
Timothy W. Isaacs
Tersia Vermeulen
James Freeman
Jean-Louis DeSousa
Riyaz Bhikoo
Doireann Hennessy
Anna Reid
Fred K. Chen
Jacqueline Bentel
Daniel McKay
R. Max Conway
Michelle R. Pereira
Bob Mirzai
Leslie Calapre
Wendy N. Erber
Melanie R. Ziman
Elin S. Gray
author_facet Aaron B. Beasley
Timothy W. Isaacs
Tersia Vermeulen
James Freeman
Jean-Louis DeSousa
Riyaz Bhikoo
Doireann Hennessy
Anna Reid
Fred K. Chen
Jacqueline Bentel
Daniel McKay
R. Max Conway
Michelle R. Pereira
Bob Mirzai
Leslie Calapre
Wendy N. Erber
Melanie R. Ziman
Elin S. Gray
author_sort Aaron B. Beasley
collection DOAJ
description (1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. (2) Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (<i>p</i> = 0.040) and overall (<i>p</i> = 0.022) survival. (4) Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.
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spelling doaj.art-e5c199c8b4d84e8186799065796429a12023-11-23T02:12:41ZengMDPI AGCancers2072-66942021-11-011323599010.3390/cancers13235990Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase CaptureAaron B. Beasley0Timothy W. Isaacs1Tersia Vermeulen2James Freeman3Jean-Louis DeSousa4Riyaz Bhikoo5Doireann Hennessy6Anna Reid7Fred K. Chen8Jacqueline Bentel9Daniel McKay10R. Max Conway11Michelle R. Pereira12Bob Mirzai13Leslie Calapre14Wendy N. Erber15Melanie R. Ziman16Elin S. Gray17School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, AustraliaPerth Retina, Subiaco, WA 6008, AustraliaAnatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital, Murdoch, WA 6150, AustraliaSchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, AustraliaCentre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Perth, WA 6000, AustraliaCentre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Perth, WA 6000, AustraliaDepartment of Ophthalmology, Royal Perth Hospital, Perth, WA 6000, AustraliaSchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, AustraliaCentre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Perth, WA 6000, AustraliaAnatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital, Murdoch, WA 6150, AustraliaRoyal Victorian Eye & Ear Hospital, Melbourne, VIC 3000, AustraliaOcular Oncology Unit, Sydney Eye Hospital and The Kinghorn Cancer Centre, Sydney, NSW 2000, AustraliaSchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, AustraliaSchool of Biomedical Sciences, University of Western Australia, Perth, WA 6000, AustraliaSchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, AustraliaSchool of Biomedical Sciences, University of Western Australia, Perth, WA 6000, AustraliaSchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, AustraliaSchool of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. (2) Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (<i>p</i> = 0.040) and overall (<i>p</i> = 0.022) survival. (4) Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.https://www.mdpi.com/2072-6694/13/23/5990uveal melanomacirculating tumour cellsliquid biopsyCTCs
spellingShingle Aaron B. Beasley
Timothy W. Isaacs
Tersia Vermeulen
James Freeman
Jean-Louis DeSousa
Riyaz Bhikoo
Doireann Hennessy
Anna Reid
Fred K. Chen
Jacqueline Bentel
Daniel McKay
R. Max Conway
Michelle R. Pereira
Bob Mirzai
Leslie Calapre
Wendy N. Erber
Melanie R. Ziman
Elin S. Gray
Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
Cancers
uveal melanoma
circulating tumour cells
liquid biopsy
CTCs
title Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
title_full Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
title_fullStr Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
title_full_unstemmed Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
title_short Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
title_sort analysis of circulating tumour cells in early stage uveal melanoma evaluation of tumour marker expression to increase capture
topic uveal melanoma
circulating tumour cells
liquid biopsy
CTCs
url https://www.mdpi.com/2072-6694/13/23/5990
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