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犬软组织肉瘤中的CD117(KIT):免疫组织化学及c-kit基因突变评估

CD117 (KIT) in canine soft tissue sarcoma: an immunohistochemical and c-kit gene mutation assessment.

作者信息

Dell'Aere Silvia, Balbi Valentina, Stefanello Damiano, Avallone Giancarlo, Ghisleni Gabriele, Perfetto Stefano, Ferrari Roberta, Auletta Luigi, Gariboldi Elisa Maria, Ubiali Alessandra, Romanello Caterina, Verdi Alessandra, Roccabianca Paola

机构信息

Department of Veterinary Medicine and Animal Sciences-DIVAS, University of Milano, Lodi, Italy.

Department of Veterinary Medical Science-DIMEVET, Bologna University, Bologna, Italy.

出版信息

Front Vet Sci. 2025 Apr 9;12:1572923. doi: 10.3389/fvets.2025.1572923. eCollection 2025.

Abstract

INTRODUCTION

Canine soft tissue sarcomas (STSs) are locally aggressive mesenchymal tumors with variable recurrence rates, and often, their therapy is limited to surgical excision. CD117 (KIT) is a tyrosine kinase receptor involved in cell growth and cancer development. c-kit proto-oncogene mutations have been reported to be associated with prognosis and therapy response in human and canine cancers. However, CD117 expression and c-kit mutations have rarely been investigated in canine STSs. This study aims to assess CD117 expression and c-kit mutations in different canine STSs.

METHODS

Spontaneous STSs were surgically removed, fixed, routinely processed, and stained for histological and anti-CD117 immunohistochemical analyses. Staining intensity and percentage of positivity were scored. Cases with intense CD117 expression in more than 50% of cells were analyzed for the presence of mutations in exons 8, 9, or 11 of the c-kit proto-oncogene.

RESULTS

Overall, 115 canine STSs were collected. Among them, CD117 was expressed in 43 STSs, with diffuse cytoplasmic staining of variable intensity. CD117 was expressed in 16 out of 27 perivascular wall tumors, 12 of 13 sarcomas of fibroblastic origin, 6 of 6 rhabdomyosarcomas, 7 of 46 liposarcomas, and 2 of 3 nerve sheath tumors. Leiomyosarcomas (20 of 20) did not show CD117 expression. Mutations were investigated in 22 cases, all of which returned negative results.

DISCUSSION

In summary, canine STSs variably expressed CD117, which suggests that tyrosine kinase inhibitors may represent a promising targeted therapy for selected canine STSs histotypes.

摘要

引言

犬软组织肉瘤(STSs)是具有不同复发率的局部侵袭性间充质肿瘤,其治疗通常限于手术切除。CD117(KIT)是一种参与细胞生长和癌症发展的酪氨酸激酶受体。据报道,c-kit原癌基因突变与人类和犬类癌症的预后及治疗反应相关。然而,犬STSs中CD117表达和c-kit突变很少被研究。本研究旨在评估不同犬STSs中CD117表达和c-kit突变情况。

方法

手术切除自发的STSs,固定,常规处理,并进行组织学和抗CD117免疫组织化学分析染色。对染色强度和阳性百分比进行评分。对超过50%的细胞中CD117表达强烈的病例分析c-kit原癌基因第8、9或11外显子的突变情况。

结果

总共收集了115例犬STSs。其中,43例STSs表达CD117,呈强度不一的弥漫性细胞质染色。27例血管周壁肿瘤中有16例表达CD117,13例成纤维细胞起源的肉瘤中有12例,6例横纹肌肉瘤全部表达,46例脂肪肉瘤中有7例,3例神经鞘瘤中有2例。平滑肌肉瘤(20例中的20例)未显示CD117表达。对22例进行了突变检测,所有结果均为阴性。

讨论

总之,犬STSs中CD117表达各异,这表明酪氨酸激酶抑制剂可能是某些犬STSs组织学类型有前景的靶向治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3089/12014545/298fcb620f6d/fvets-12-1572923-g001.jpg

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