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

SIMPLE SUMMARY: Approximately 50% of patients with uveal melanoma will develop incurable metastatic disease. This can be predicted, but requires a biopsy of the eye, which outside of centres of excellence, are not routinely performed. Given that uveal melanoma spreads through the blood, utilising ci...

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Autores principales: Beasley, Aaron B., Isaacs, Timothy W., Vermeulen, Tersia, Freeman, James, DeSousa, Jean-Louis, Bhikoo, Riyaz, Hennessy, Doireann, Reid, Anna, Chen, Fred K., Bentel, Jacqueline, McKay, Daniel, Conway, R. Max, Pereira, Michelle R., Mirzai, Bob, Calapre, Leslie, Erber, Wendy N., Ziman, Melanie R., Gray, Elin S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657240/
https://www.ncbi.nlm.nih.gov/pubmed/34885099
http://dx.doi.org/10.3390/cancers13235990
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author Beasley, Aaron B.
Isaacs, Timothy W.
Vermeulen, Tersia
Freeman, James
DeSousa, Jean-Louis
Bhikoo, Riyaz
Hennessy, Doireann
Reid, Anna
Chen, Fred K.
Bentel, Jacqueline
McKay, Daniel
Conway, R. Max
Pereira, Michelle R.
Mirzai, Bob
Calapre, Leslie
Erber, Wendy N.
Ziman, Melanie R.
Gray, Elin S.
author_facet Beasley, Aaron B.
Isaacs, Timothy W.
Vermeulen, Tersia
Freeman, James
DeSousa, Jean-Louis
Bhikoo, Riyaz
Hennessy, Doireann
Reid, Anna
Chen, Fred K.
Bentel, Jacqueline
McKay, Daniel
Conway, R. Max
Pereira, Michelle R.
Mirzai, Bob
Calapre, Leslie
Erber, Wendy N.
Ziman, Melanie R.
Gray, Elin S.
author_sort Beasley, Aaron B.
collection PubMed
description SIMPLE SUMMARY: Approximately 50% of patients with uveal melanoma will develop incurable metastatic disease. This can be predicted, but requires a biopsy of the eye, which outside of centres of excellence, are not routinely performed. Given that uveal melanoma spreads through the blood, utilising circulating tumour cells from the blood might provide an alternative minimally invasive method to avoid the biopsy. However, the clinical application hinges on the detection rate of circulating tumour cells. Herein we assessed markers to improve the capture and detection of uveal melanoma circulating tumour cells and found that they could be detected in 86% of patients. We further found that ≥3 circulating tumour cells was significantly associated with worse survival. ABSTRACT: (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 (p = 0.040) and overall (p = 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 pubmed-86572402021-12-10 Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture Beasley, Aaron B. Isaacs, Timothy W. Vermeulen, Tersia Freeman, James DeSousa, Jean-Louis Bhikoo, Riyaz Hennessy, Doireann Reid, Anna Chen, Fred K. Bentel, Jacqueline McKay, Daniel Conway, R. Max Pereira, Michelle R. Mirzai, Bob Calapre, Leslie Erber, Wendy N. Ziman, Melanie R. Gray, Elin S. Cancers (Basel) Article SIMPLE SUMMARY: Approximately 50% of patients with uveal melanoma will develop incurable metastatic disease. This can be predicted, but requires a biopsy of the eye, which outside of centres of excellence, are not routinely performed. Given that uveal melanoma spreads through the blood, utilising circulating tumour cells from the blood might provide an alternative minimally invasive method to avoid the biopsy. However, the clinical application hinges on the detection rate of circulating tumour cells. Herein we assessed markers to improve the capture and detection of uveal melanoma circulating tumour cells and found that they could be detected in 86% of patients. We further found that ≥3 circulating tumour cells was significantly associated with worse survival. ABSTRACT: (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 (p = 0.040) and overall (p = 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. MDPI 2021-11-28 /pmc/articles/PMC8657240/ /pubmed/34885099 http://dx.doi.org/10.3390/cancers13235990 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Beasley, Aaron B.
Isaacs, Timothy W.
Vermeulen, Tersia
Freeman, James
DeSousa, Jean-Louis
Bhikoo, Riyaz
Hennessy, Doireann
Reid, Anna
Chen, Fred K.
Bentel, Jacqueline
McKay, Daniel
Conway, R. Max
Pereira, Michelle R.
Mirzai, Bob
Calapre, Leslie
Erber, Wendy N.
Ziman, Melanie R.
Gray, Elin S.
Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657240/
https://www.ncbi.nlm.nih.gov/pubmed/34885099
http://dx.doi.org/10.3390/cancers13235990
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