全面手术切除对于人类、狗和猫的软组织肉瘤 (STS) 管理来说至关重要。近红外靶向示踪剂荧光引导手术 (FGS) 可以促进术中对肿瘤的可视化，提高切除的准确性。由于肿瘤罕见且异质性高，STS 的靶点鉴定相当复杂。本研究旨在验证选定的人类、狗和猫 STS 亚型中的成纤维细胞激活蛋白 alpha (FAP) 的表达，以评估 FAP 作为 FGS 靶点的价值，并验证伴侣动物是否适合作为翻译模型。我们通过免疫组织化学染色对53例狗 STS (包括血管周围肿瘤 (PWT)、狗纤维肉瘤 (cFS) 和未进一步分型的 STS)、24例猫纤维肉瘤和39例人类 STS (粘液纤维肉瘤、未分化多形性肉瘤、皮脂纤维肉瘤和恶性周围神经鞘瘤) 进行了固定后石蜡包埋组织样本的 FAP 表达染色。我们使用目视评估的半定量表达评分和数字图像分析来定量测定肿瘤、周围肿瘤、健康皮肤和炎症组织样本中的 FAP 标记。随后依据之前的方法进行了 TASC 指标评分。85%的人类 STS (33/39)、76%的狗 STS (40/53) 和92%的猫 STS (22/24) 的肿瘤细胞中显示超过10%的 FAP 阳性表达。在53%的狗 STS (28/53)、67%的猫 STS (16/24) 和44%的人类 STS (17/39) 中确定了高表达。狗、猫和人类 STS 的平均 FAP 标记面积分别为31%、33%和42% (p > 0.8990)。与健康组织样本和周围肿瘤组织样本相比，STS 的 FAP 阳性肿瘤面积更大 (p < 0.0001)。所有猫和人类 STS 亚型以及狗 PWT 的 TASC 分数均超过18，但对于狗 STS NOS 和 cFS 却未能达到该标准。本研究首次跨物种评估了 FAP 在 STS 中的靶点价值。我们的研究结果表明，与非癌组织相比，FAP 在多种 STS 亚型中的表达增加，并因此验证了狗和猫作为合适的动物模型。根据 TASC 分数，FAP 可以被考虑作为 FGS 的靶点。 版权所有© 2023 Beer, Pauli, Haberecker, Grest, Beebe, Fuchs, Markkanen, Krudewig and Nolff。

Complete surgical tumor resection is paramount in the management of soft tissue sarcoma (STS) in humans, dogs, and cats alike. Near-infrared targeted tracers for fluorescence-guided surgery (FGS) could facilitate intraoperative visualization of the tumor and improve resection accuracy. Target identification is complicated in STS due to the rarity and heterogeneity of the disease. This study aims to validate the expression of fibroblast activation protein alpha (FAP) in selected human, canine, and feline STS subtypes to assess the value of FAP as a target for FGS and to validate companion animals as a translational model.Formalin-fixed and paraffin-embedded tissue samples from 53 canine STSs (perivascular wall tumor (PWT), canine fibrosarcoma (cFS), and STS not further specified (NOS)), 24 feline fibrosarcomas, and 39 human STSs (myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor) as well as six canine and seven feline healthy controls and 10 inflamed tissue samples were immunohistochemically stained for their FAP expression. FAP labeling in tumor, peritumoral, healthy skin, and inflamed tissue samples was quantified using a visually assessed semiquantitative expression score and digital image analysis. Target selection criteria (TASC) scoring was subsequently performed as previously described.Eighty-five percent (85%) of human (33/39), 76% of canine (40/53), and 92% of feline (22/24) STSs showed FAP positivity in over 10% of the tumor cells. A high expression was determined in 53% canine (28/53), 67% feline (16/24), and 44% human STSs (17/39). The average FAP-labeled area of canine, feline, and human STSs was 31%, 33%, and 42%, respectively (p > 0.8990). The FAP-positive tumor area was larger in STS compared to healthy and peritumoral tissue samples (p < 0.0001). TASC scores were above 18 for all feline and human STS subtypes and canine PWTs but not for canine STS NOS and cFS.This study represents the first cross-species target evaluation of FAP for STS. Our results demonstrate that FAP expression is increased in various STS subtypes compared to non-cancerous tissues across species, thereby validating dogs and cats as suitable animal models. Based on a TASC score, FAP could be considered a target for FGS.Copyright © 2023 Beer, Pauli, Haberecker, Grest, Beebe, Fuchs, Markkanen, Krudewig and Nolff.