Erdogan Ezgi Genc, Yalta Tülin D, Can Nuray, Süt Necdet, Taştekin Ebru, Usta Ufuk, Puyan Fulya Öz, Usturalı Keskin Fatma E, Kurt Busem B
Department of Pathology, Faculty of Medicine, Trakya University, Edirne; Department of Pathology, Lüleburgaz State Hospital, Kırklareli, Turkey.
Department of Pathology, Faculty of Medicine, Trakya University, Edirne, Turkey.
Indian J Pathol Microbiol. 2023 Jul-Sep;66(3):449-455. doi: 10.4103/ijpm.ijpm_777_21.
Uterine carcinosarcomas (UCS) constitute 3-4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms.
In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS.
In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method.
EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development.
This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.
子宫癌肉瘤（UCS）占所有子宫恶性肿瘤的3%-4%，占子宫肿瘤所致死亡的16%。
在本研究中，我们旨在对12个基因（KRAS、NRAS、EGFR、C-KIT、BRAF、PDGFRA、ALK、ERBB2、ERBB3、ESR1、RAF1、PIK3CA）进行基于DNA的突变分析，以使用下一代测序（NGS）确定侵袭性UCS和预后不良患者的UCS分子亚型。我们旨在将分析结果与临床病理数据进行比较，以促进与UCS分子变化相关的靶向治疗方法的发展。
在本研究中，我们纳入了12例诊断为子宫癌肉瘤的病例，并检查了在UCS发病机制中起作用的癌基因的变化。为了分析突变，使用NGS方法将临床病理数据与由12个基因和1237个UCS变体组成的基于DNA的基因面板中的变异进行比较。
91.7%的病例中发现EGFR突变，41.7%的病例中发现突变，25%的病例中发现PDGFRA突变，16.7%的病例中发现KRAS和PIK3CA突变，8.3%的病例中发现C-KIT突变。虽然在检测到的突变与临床病理数据之间未发现统计学意义，但得出结论认为PDGFRA突变可能与晚期疾病发展相关。
本研究关于UCS不同分子类型的发现以及UCS肿瘤发生的信息，可通过识别代表早期致癌事件的可靶向突变，为未来的靶向治疗提供推断，从而有助于对此主题的进一步研究。
