Immunohistochemical Evaluation of Candidate Biomarkers for Fluorescence-Guided Surgery of Myxofibrosarcoma Using an Objective Scoring Method

被引:4
作者
Rijs, Zeger [1 ]
Belt, Esther [1 ]
Kalisvaart, Gijsbert M. M. [2 ]
Sier, Cornelis F. M. [3 ,4 ]
Kuppen, Peter J. K. [3 ]
Cleven, Arjen H. G. [5 ,6 ]
Vahrmeijer, Alexander L. L. [3 ]
van de Sande, Michiel A. J. [1 ]
van Driel, Pieter B. A. A. [7 ]
机构
[1] Leiden Univ, Med Ctr, Dept Orthoped Surg, NL-2333 ZA Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Radiol, NL-2333 ZA Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Surg, NL-2333 ZA Leiden, Netherlands
[4] Percuros BV, Zernikedreef 8, NL-2333 CL Leiden, Netherlands
[5] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZA Leiden, Netherlands
[6] Univ Med Ctr Groningen, Dept Pathol, NL-9700 RB Groningen, Netherlands
[7] Isala Hosp, Dept Orthoped Surg, NL-8025 AB Zwolle, Netherlands
基金
欧盟地平线“2020”;
关键词
soft tissue sarcoma; molecular imaging; immunohistochemistry; fluorescence-guided surgery; tumor endothelial marker-1; SOFT-TISSUE; PROGNOSTIC-FACTORS; ENDOSIALIN TEM1; HIGH-GRADE; SARCOMA; EXPRESSION; MARKER; SURVIVAL; SYSTEMS; CD248;
D O I
10.3390/biomedicines11030982
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-alpha (PDGFR-alpha), 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-alpha 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-alpha, regardless of preoperative therapy. Conclusion: TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.
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页数:12
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