Cargando…

Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes

OBJECTIVE: Fifty percent of patients with high-grade serous ovarian cancer harbor defects in the homologous recombination repair pathway. RAD51 foci form where DNA is damaged, indicating its involvement in repairing double-stranded breaks. High levels of RAD51 in ovarian cancer tissue have been asso...

Descripción completa

Detalles Bibliográficos
Autores principales: Alizzi, Zena, Saravi, Sayeh, Khalique, Saira, McDonald, Thirza, Karteris, Emmanouil, Hall, Marcia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511972/
https://www.ncbi.nlm.nih.gov/pubmed/37541687
http://dx.doi.org/10.1136/ijgc-2023-004483
_version_ 1785108263027605504
author Alizzi, Zena
Saravi, Sayeh
Khalique, Saira
McDonald, Thirza
Karteris, Emmanouil
Hall, Marcia
author_facet Alizzi, Zena
Saravi, Sayeh
Khalique, Saira
McDonald, Thirza
Karteris, Emmanouil
Hall, Marcia
author_sort Alizzi, Zena
collection PubMed
description OBJECTIVE: Fifty percent of patients with high-grade serous ovarian cancer harbor defects in the homologous recombination repair pathway. RAD51 foci form where DNA is damaged, indicating its involvement in repairing double-stranded breaks. High levels of RAD51 in ovarian cancer tissue have been associated with a poorer prognosis. OBJECTIVE: To demonstrate RAD51 foci in circulating cancer-associated cells of patients with ovarian cancer and their association with clinical outcomes. METHODS: One hundred and twenty-four patients with high-grade serous ovarian cancer had blood samples taken at strategic points during treatment and follow-up. Cells were stained using WT1 and RAD51 antibodies with immunofluorescence and reviewed under Leica camera microscopy; RAD51 foci were counted. Correlations were made between numbers of RAD51 foci and treatment response, BRCA status, and progression-free survival. RESULTS: RAD51 foci were identified in all patients (n=42) with wild-type BRCA. BRCA mutant/homologous recombination deficiency-positive patients (n=8) had significantly lower numbers of RAD51 foci (p=0.009). Responders to treatment (n=32) had a reduction in circulating cells (p=0.02) and RAD51 foci (p=0.0007). Numbers of RAD51 foci were significantly higher in the platinum-resistant population throughout treatment: at the start of treatment, in 56 platinum-sensitive patients there was a mean of 3.6 RAD51 foci versus 6.2 in 15 platinum-resistant patients (p=0.02). Patients with a high number of RAD51 foci had worse median progression-free survival: in 39 patients with a mean of <3 RAD51 foci at treatment start, median progression-free survival had not been reached, compared with 32 patients with >3 RAD51 foci whose progression-free survival was 13 months (p=0.04). CONCLUSIONS: Levels of RAD51 foci in circulating cancer-associated cells of patients with high-grade serous ovarian cancer are associated with clinical outcomes and may be a more pragmatic method of determining a homologous repair-deficient population.
format Online
Article
Text
id pubmed-10511972
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-105119722023-09-22 Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes Alizzi, Zena Saravi, Sayeh Khalique, Saira McDonald, Thirza Karteris, Emmanouil Hall, Marcia Int J Gynecol Cancer Original Research OBJECTIVE: Fifty percent of patients with high-grade serous ovarian cancer harbor defects in the homologous recombination repair pathway. RAD51 foci form where DNA is damaged, indicating its involvement in repairing double-stranded breaks. High levels of RAD51 in ovarian cancer tissue have been associated with a poorer prognosis. OBJECTIVE: To demonstrate RAD51 foci in circulating cancer-associated cells of patients with ovarian cancer and their association with clinical outcomes. METHODS: One hundred and twenty-four patients with high-grade serous ovarian cancer had blood samples taken at strategic points during treatment and follow-up. Cells were stained using WT1 and RAD51 antibodies with immunofluorescence and reviewed under Leica camera microscopy; RAD51 foci were counted. Correlations were made between numbers of RAD51 foci and treatment response, BRCA status, and progression-free survival. RESULTS: RAD51 foci were identified in all patients (n=42) with wild-type BRCA. BRCA mutant/homologous recombination deficiency-positive patients (n=8) had significantly lower numbers of RAD51 foci (p=0.009). Responders to treatment (n=32) had a reduction in circulating cells (p=0.02) and RAD51 foci (p=0.0007). Numbers of RAD51 foci were significantly higher in the platinum-resistant population throughout treatment: at the start of treatment, in 56 platinum-sensitive patients there was a mean of 3.6 RAD51 foci versus 6.2 in 15 platinum-resistant patients (p=0.02). Patients with a high number of RAD51 foci had worse median progression-free survival: in 39 patients with a mean of <3 RAD51 foci at treatment start, median progression-free survival had not been reached, compared with 32 patients with >3 RAD51 foci whose progression-free survival was 13 months (p=0.04). CONCLUSIONS: Levels of RAD51 foci in circulating cancer-associated cells of patients with high-grade serous ovarian cancer are associated with clinical outcomes and may be a more pragmatic method of determining a homologous repair-deficient population. BMJ Publishing Group 2023-09 2023-08-04 /pmc/articles/PMC10511972/ /pubmed/37541687 http://dx.doi.org/10.1136/ijgc-2023-004483 Text en © IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research
Alizzi, Zena
Saravi, Sayeh
Khalique, Saira
McDonald, Thirza
Karteris, Emmanouil
Hall, Marcia
Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes
title Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes
title_full Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes
title_fullStr Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes
title_full_unstemmed Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes
title_short Identification of RAD51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes
title_sort identification of rad51 foci in cancer-associated circulating cells of patients with high-grade serous ovarian cancer: association with treatment outcomes
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511972/
https://www.ncbi.nlm.nih.gov/pubmed/37541687
http://dx.doi.org/10.1136/ijgc-2023-004483
work_keys_str_mv AT alizzizena identificationofrad51fociincancerassociatedcirculatingcellsofpatientswithhighgradeserousovariancancerassociationwithtreatmentoutcomes
AT saravisayeh identificationofrad51fociincancerassociatedcirculatingcellsofpatientswithhighgradeserousovariancancerassociationwithtreatmentoutcomes
AT khaliquesaira identificationofrad51fociincancerassociatedcirculatingcellsofpatientswithhighgradeserousovariancancerassociationwithtreatmentoutcomes
AT mcdonaldthirza identificationofrad51fociincancerassociatedcirculatingcellsofpatientswithhighgradeserousovariancancerassociationwithtreatmentoutcomes
AT karterisemmanouil identificationofrad51fociincancerassociatedcirculatingcellsofpatientswithhighgradeserousovariancancerassociationwithtreatmentoutcomes
AT hallmarcia identificationofrad51fociincancerassociatedcirculatingcellsofpatientswithhighgradeserousovariancancerassociationwithtreatmentoutcomes