Mohammed Mona M, Hafez Hanafy A, Elnadi Enas M, Salama Asmaa I, Abd Elaziz Abd Elaziz Saad, Ahmed Gehad T, ELwakeel Madeeha A, Kamal Mohamed K, Kieran Mark W, Elhaddad Alaa M
Department of Pediatric Oncology, Children Cancer Hospital (57357), Cairo, Egypt.
Department of Pediatric Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
Front Oncol. 2024 Oct 29;14:1480773. doi: 10.3389/fonc.2024.1480773. eCollection 2024.
Activated vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs) and c-Kit have been shown to be involved in the growth, invasion and metastasis of non-rhabdomyosarcoma soft tissue sarcoma tumor (NRSTS) with promising results for targeted therapy. Our aim was to assess the expression of these markers among different histological types and correlate with outcomes.
This retrospective study included pediatric patients aged ≤ 18 years diagnosed with high-grade NRSTS who were treated at Children Cancer Hospital Egypt 57357 as per the COG NRSTS protocol (ARST0332). Expression of VEGFR2, PDGFRs (α and β) and c-Kit in tumor tissue was assessed by immunohistochemistry and correlated with clinical outcome.
Of 113 patients, 96 were eligible for the analysis with a median age of 11 years. Overall, 32.3% demonstrated high expression of PDGFRα, 17.7% for PDGFRβ, 19.8% for VEGFR2 and 8.3% exhibited positive expression for c-kit on the tumor cells. Most cases of synovial sarcoma (45.8%) and 43.7% of patients with undifferentiated sarcoma exhibited high expression of PDGFRα while 41.6% of MPNST showed high expression to PDGFRβ. The 5-year overall survival (OS), event free survival and relapse free survival (RFS) for the whole cohort were 59%, 54% and 60% respectively. In univariate analyses, only PDGFRα had a negative prognostic impact on relapse free survival (RFS) (=0.03). In multivariate analyses, VEGFR2 was found to have a negative prognostic impact for OS ( = 0.02).
Our findings indicated that tyrosine kinase receptors are upregulated in NRSTS and exhibited a distinct expression pattern within various subgroups. High expression of VEGFR2 and PDGFRα significantly correlated with reduced survival and may guide targeted therapy approaches for this poor prognosis group of patients.
活化的血管内皮生长因子受体（VEGFRs）、血小板衍生生长因子受体（PDGFRs）和c-Kit已被证明参与非横纹肌肉瘤软组织肉瘤肿瘤（NRSTS）的生长、侵袭和转移，靶向治疗取得了有前景的结果。我们的目的是评估这些标志物在不同组织学类型中的表达，并与预后相关联。
这项回顾性研究纳入了年龄≤18岁、诊断为高级别NRSTS的儿科患者，这些患者在埃及儿童癌症医院57357按照儿童肿瘤协作组NRSTS方案（ARST0332）接受治疗。通过免疫组织化学评估肿瘤组织中VEGFR2、PDGFRs（α和β）和c-Kit的表达，并与临床结果相关联。
113例患者中，96例符合分析条件，中位年龄为11岁。总体而言，32.3%的患者肿瘤细胞中PDGFRα呈高表达，17.7%为PDGFRβ，19.8%为VEGFR2，8.3%的患者c-kit呈阳性表达。大多数滑膜肉瘤病例（45.8%）和43.7%的未分化肉瘤患者PDGFRα呈高表达，而41.6%的恶性周围神经鞘膜瘤PDGFRβ呈高表达。整个队列的5年总生存率（OS）、无事件生存率和无复发生存率（RFS）分别为59%、54%和60%。在单因素分析中，只有PDGFRα对无复发生存率（RFS）有负面预后影响（P=0.03）。在多因素分析中，发现VEGFR2对总生存率（OS）有负面预后影响（P=0.02）。
我们的研究结果表明，酪氨酸激酶受体在NRSTS中上调，并且在各个亚组中表现出不同的表达模式。VEGFR2和PDGFRα的高表达与生存率降低显著相关，可能为这一预后不良的患者群体指导靶向治疗方法。
