Rijs Zeger, Belt Esther, Kalisvaart Gijsbert M, Sier Cornelis F M, Kuppen Peter J K, Cleven Arjen H G, Vahrmeijer Alexander L, van de Sande Michiel A J, van Driel Pieter B A A
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.
Biomedicines. 2023 Mar 22;11(3):982. doi: 10.3390/biomedicines11030982.
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).
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.
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.
TEM-1-targeted FGS tracers should be further investigated to optimize MFS treatment.
黏液纤维肉瘤（MFS）是老年患者中最常见的软组织肉瘤亚型。局部复发（LR）仍然是一个主要问题，因为缺乏术中指导以及肿瘤呈浸润性生长模式且有细长的尾巴，这妨碍了外科医生为MFS获得足够的切除边缘。荧光引导手术（FGS）可以通过在手术过程中勾勒肿瘤组织来克服这一问题。成功进行FGS的最重要步骤之一是定义一种肿瘤特异性生物标志物，该标志物在肿瘤组织中高度过表达，而在相邻健康组织中低表达或不表达。本研究的目的是使用免疫组织化学（IHC）评估先前选择的八种有前景的FGS生物标志物在MFS组织样本及其相邻健康组织中的表达情况。
在17个石蜡包埋的MFS样本中对以下八种生物标志物进行染色：肿瘤内皮标志物-1（TEM-1，也称为内唾液酸蛋白/CD248）、血管内皮生长因子受体-1（VEGFR-1，也称为Flt-1）、血管内皮生长因子受体-2（VEGFR-2，也称为Flk1）、血管内皮生长因子-A（VEGF-A）、表皮生长因子受体（EGFR）、胰岛素样生长因子-1受体（IGF-1R）、血小板衍生生长因子受体-α（PDGFR-α）和分化簇40（CD40，也称为TNFRSF5）。一位专门研究肉瘤的病理学家标注了每个MFS组织样本中肿瘤与相邻健康组织之间的边界。随后，我们使用一种客观的IHC评分方法来评估和比较肿瘤与相邻健康组织之间染色强度的差异，这对于FGS的应用至关重要。
TEM-1、VEGF-A和PDGFR-α在所有MFS肿瘤中均有染色，而其他生物标志物并非在所有MFS肿瘤中都有表达。最终，基于与VEGF-A和PDGFR-α相比更高的肿瘤与背景（TBR）染色强度，无论术前治疗情况如何，TEM-1被确定为MFS中FGS最合适的生物标志物。
应进一步研究针对TEM-1的FGS示踪剂，以优化MFS治疗。
