Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours

Background: There are limited treatment options for patients with advanced or metastatic gastrointestinal stromal tumours (GISTs) that lack mutations targetable by tyrosine kinase inhibitors (TKIs) or that have developed resistance to TKIs. Gastrin-releasing peptide receptor (GRPR) theranostics may...

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Main Authors: M. Berndsen, F. Puls, A. Thornell, Y. Arvidsson, A. Muth, S. Lindskog, E. Elias
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:ESMO Gastrointestinal Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2949819824000669
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author M. Berndsen
F. Puls
A. Thornell
Y. Arvidsson
A. Muth
S. Lindskog
E. Elias
author_facet M. Berndsen
F. Puls
A. Thornell
Y. Arvidsson
A. Muth
S. Lindskog
E. Elias
author_sort M. Berndsen
collection DOAJ
description Background: There are limited treatment options for patients with advanced or metastatic gastrointestinal stromal tumours (GISTs) that lack mutations targetable by tyrosine kinase inhibitors (TKIs) or that have developed resistance to TKIs. Gastrin-releasing peptide receptor (GRPR) theranostics may offer a viable option in GISTs. However, the expression of the GRPR in GIST has not been extensively studied. Materials and methods: GRPR expression was evaluated using immunohistochemistry in two separate tissue microarrays from patients treated at Sahlgrenska University Hospital, one from the pre-TKI era (1983-2001) and the other from the post-TKI era (2014-2020). In total, 205 tumour samples were characterized as having low/none or moderate/high expression of the GRPR, and these were correlated with clinical characteristics and survival outcomes. Results: In total, 80% of the tumour samples exhibited moderate or high expression of GRPR. GRPR expression was not associated with gender, age, tumour location, or risk group, as defined by the modified National Institutes of Health (NIH) consensus criteria. Neoadjuvant treatment with TKI was correlated with low/none GRPR expression (P = 0.04). In patients who underwent surgery with curative intent and did not receive neoadjuvant treatment, GRPR expression was not associated with survival outcomes. Conclusions: This study is the first to investigate GRPR expression in a large cohort of GIST tumours. Our results demonstrate that most GIST tumours exhibit a moderate to high expression of the receptor, suggesting that GRPR theranostics could be a viable option for TKI-resistant GIST. Interestingly, tumours that were pretreated with TKI showed lower expression levels of GRPR, indicating a need for further studies to explore this finding.
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spelling doaj-art-79bcba9d0c914c6fac7fa299b9a6c93f2024-12-17T05:02:28ZengElsevierESMO Gastrointestinal Oncology2949-81982024-12-016100105Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumoursM. Berndsen0F. Puls1A. Thornell2Y. Arvidsson3A. Muth4S. Lindskog5E. Elias6Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Correspondence to: Dr Marta Berndsen, Kirurg mottagningen, Blå stråket 5, 413 45 Gothenburg, Sweden. Tel: +46735875442Department of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Clinical Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Laboratory Medicine, Sahlgrenska Center for Cancer Research, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Halland Hospital, Varberg, SwedenDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, SwedenBackground: There are limited treatment options for patients with advanced or metastatic gastrointestinal stromal tumours (GISTs) that lack mutations targetable by tyrosine kinase inhibitors (TKIs) or that have developed resistance to TKIs. Gastrin-releasing peptide receptor (GRPR) theranostics may offer a viable option in GISTs. However, the expression of the GRPR in GIST has not been extensively studied. Materials and methods: GRPR expression was evaluated using immunohistochemistry in two separate tissue microarrays from patients treated at Sahlgrenska University Hospital, one from the pre-TKI era (1983-2001) and the other from the post-TKI era (2014-2020). In total, 205 tumour samples were characterized as having low/none or moderate/high expression of the GRPR, and these were correlated with clinical characteristics and survival outcomes. Results: In total, 80% of the tumour samples exhibited moderate or high expression of GRPR. GRPR expression was not associated with gender, age, tumour location, or risk group, as defined by the modified National Institutes of Health (NIH) consensus criteria. Neoadjuvant treatment with TKI was correlated with low/none GRPR expression (P = 0.04). In patients who underwent surgery with curative intent and did not receive neoadjuvant treatment, GRPR expression was not associated with survival outcomes. Conclusions: This study is the first to investigate GRPR expression in a large cohort of GIST tumours. Our results demonstrate that most GIST tumours exhibit a moderate to high expression of the receptor, suggesting that GRPR theranostics could be a viable option for TKI-resistant GIST. Interestingly, tumours that were pretreated with TKI showed lower expression levels of GRPR, indicating a need for further studies to explore this finding.http://www.sciencedirect.com/science/article/pii/S2949819824000669gastrointestinal stromal tumourgastrin-releasing peptidetissue microarraypeptide receptor radioligand therapy
spellingShingle M. Berndsen
F. Puls
A. Thornell
Y. Arvidsson
A. Muth
S. Lindskog
E. Elias
Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours
ESMO Gastrointestinal Oncology
gastrointestinal stromal tumour
gastrin-releasing peptide
tissue microarray
peptide receptor radioligand therapy
title Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours
title_full Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours
title_fullStr Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours
title_full_unstemmed Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours
title_short Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours
title_sort gastrin releasing peptide receptor expression in gastrointestinal stromal tumours
topic gastrointestinal stromal tumour
gastrin-releasing peptide
tissue microarray
peptide receptor radioligand therapy
url http://www.sciencedirect.com/science/article/pii/S2949819824000669
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