Evaluation of Potential Targets for Fluorescence-Guided Surgery in Pediatric Ewing Sarcoma: A Preclinical Proof-of-Concept Study.

Autor: Jeremiasse B; Department of Surgery, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Rijs Z; Department of Orthopedic Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Angoelal KR; Department of Surgery, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Hiemcke-Jiwa LS; Department of Pathology, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.; Department of Pathology, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands., de Boed EA; Department of Pathology, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Kuppen PJK; Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Sier CFM; Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., van Driel PBAA; Department of Orthopedic Surgery, Isala Hospital, 8025 AB Zwolle, The Netherlands., van de Sande MAJ; Department of Surgery, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.; Department of Orthopedic Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Wijnen MHWA; Department of Surgery, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Rios AC; Research Department, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, The Netherlands., van der Steeg AFW; Department of Surgery, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Jul 31; Vol. 15 (15). Date of Electronic Publication: 2023 Jul 31.
DOI: 10.3390/cancers15153896
Abstrakt: Fluorescence-guided surgery (FGS), based on fluorescent tracers binding to tumor-specific biomarkers, could assist surgeons to achieve complete tumor resections. This study evaluated potential biomarkers for FGS in pediatric Ewing sarcoma (ES). Immunohistochemistry (IHC) was performed to assess CD99, CXCR4, CD117, NPY-R-Y1, and IGF-1R expression in ES biopsies and resection specimens. LINGO-1 and GD2 evaluation did not work on the acquired tissue. Based on the immunoreactive scores, anti-CD99 and anti-CD117 were evaluated for binding specificity using flow cytometry and immunofluorescence microscopy. Anti-GD2, a tracer in the developmental phase, was also tested. These three tracers were topically applied to a freshly resected ES tumor and adjacent healthy tissue. IHC demonstrated moderate/strong CD99 and CD117 expression in ES tumor samples, while adjacent healthy tissue had limited expression. Flow cytometry and immunofluorescence microscopy confirmed high CD99 expression, along with low/moderate CD117 and low GD2 expression, in ES cell lines. Topical anti-CD99 and anti-GD2 application on ES tumor showed fluorescence, while anti-CD117 did not show fluorescence for this patient. In conclusion, CD99-targeting tracers hold promise for FGS of ES. CD117 and GD2 tracers could be potential alternatives. The next step towards development of ES-specific FGS tracers could be ex vivo topical application experiments on a large cohort of ES patients.
Databáze: MEDLINE
Nepřihlášeným uživatelům se plný text nezobrazuje