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© 2023 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Introduction: Myxofibrosarcoma (MFS) is the most common soft-tissue sarcoma subtype in elderly patients. Local recurrence (LR) remains a major concern as the lack of intraoperative guidance and an infiltrative growth pattern with long, slender tails hamper surgeons’ ability to achieve adequate resection margins for MFS. Fluorescence-guided surgery (FGS) could overcome this concern by delineating tumor tissue during surgery. One of the most important steps to successful FGS is to define a tumor-specific biomarker that is highly overexpressed in tumor tissue while low or absent in adjacent healthy tissue. The aim of this study is to evaluate the expression of eight previously selected promising biomarkers for FGS in MFS tissue samples with adjacent healthy tissue using immunohistochemistry (IHC). Methods: The following eight biomarkers were stained in seventeen paraffin-embedded MFS samples: tumor endothelial marker-1 (TEM-1, also known as endosialin/CD248), vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1), vascular endothelial growth factor receptor-2 (VEGFR-2, also known as Flk1), vascular endothelial growth factor-A (VEGF-A), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), platelet derived growth factor receptor-α (PDGFR-α), and cluster of differentiation 40 (CD40, also known as TNFRSF5). A pathologist specializing in sarcoma annotated the margin between the tumor and adjacent healthy tissue in each MFS tissue sample. Subsequently, we used an objective IHC scoring method to assess and compare the difference in staining intensity between the tumor and adjacent healthy tissue, which is crucial for the use of FGS. Results: TEM-1, VEGF-A, and PDGFR-α stained all MFS tumors, while the other biomarkers did not show expression in all MFS tumors. Ultimately, TEM-1 was identified as the most suitable biomarker for FGS in MFS based on higher tumor-to-background (TBR) staining intensity compared to VEGF-A and PDGFR-α, regardless of preoperative therapy. Conclusion: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.

Details

Title
Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method
Author
Zeger Rijs 1   VIAFID ORCID Logo  ; Belt, Esther 1 ; Kalisvaart, Gijsbert M 2   VIAFID ORCID Logo  ; Sier, Cornelis F M 3   VIAFID ORCID Logo  ; Kuppen, Peter J K 4   VIAFID ORCID Logo  ; Cleven, Arjen H G 5 ; Vahrmeijer, Alexander L 4 ; Michiel A J van de Sande 1   VIAFID ORCID Logo  ; Pieter B A A van Driel 6 

 Department of Orthopedic Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands 
 Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands 
 Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Percuros BV, Zernikedreef 8, 2333 CL Leiden, The Netherlands 
 Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands 
 Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Department of Pathology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands 
 Department of Orthopedic Surgery, Isala Hospital, 8025 AB Zwolle, The Netherlands 
First page
982
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
22279059
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2791585594
Copyright
© 2023 by the authors. 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/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.