Uterin karsinosarkomların moleküler analizi
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Dosyalar
Tarih
2019
Yazarlar
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Yayıncı
Trakya Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Endometrial karsinosarkomlar, yüksek dereceli karsinom ve sarkomatöz elementlerden oluşan, nadir görülen fakat; oldukça agresif neoplazilerdir. Bu tümörlerin patogenezindeki genetik değişiklikler iyi bilinmemektedir. Endometrial karsinosarkomların patogenezinde rol oynayan onkojenlerdeki değişiklikleri analiz ettiğimiz çalışmamızda, NGS yöntemi ile karsinosarkomlarda 12 gen 1237 varyanttan oluşan gen panelindeki varyasyonlar ile klinikopatolojik verilerin karşılaştırılması amaçlandı. Trakya Üniversitesi Tıp Fakültesi Tıbbi Patoloji Anabilim Dalı arşivinden uterus yerleşimli karsinosarkom tanısı alan 12 adet olgu dahil edildi. Olgulara ait H&E kesitleri ışık mikroskobunda incelendi. Olgular, güncel sınıflandırılmaya (DSÖ) göre değerlendirilerek histolojik alt tiplendirme yapıldı. Heterolog eleman varlığı, myometrial invazyon derinliği, lenfovasküker invazyonu, diğer doku/organlara yayılım değerlendirildi. Olguların %91,7’sinde EGFR, %41,7’inde ERBB2, %25’inde PDGFRA, %16,7’sinde KRAS ve PIK3CA, %8,3’ünde C-KİT mutasyonu saptandı. Endometrial karsinosarkomların da endometrial karsinomlarda görülen heterojenliğe benzer şekilde, heterojen moleküler özellikler sergilediği sonucuna varıldı. Saptanan gen mutasyonları ile klinikopatolojik veriler arasında istatiksel anlamlılık saptanmamış olsa da PDGFRA gen mutasyonunun myometrial invazyon derinliği, lenfatik invazyon ve heterolog eleman varlığı ile ilişkili olabileceği sonucuna varıldı. Sonuç olarak, çalışmamızda tespit ettiğimiz EGFR ve ERBB2 varyasyonlarının, KS’ların patogenezisinde sürücü mutasyon rolü olup olmadığının, tirozin kinaz inhibitörlerinin bu varyasyonları hedefleyebilme potansiyeli ile ilgili daha geniş vaka serileri ile yapılacak çalışmalara ihtiyaç vardır. Karsinosarkomlarda en dikkat çekici mutasyonlardan biri olan PIK3CA ve KRAS gen mutasyonu ise çalışmamızda 2 olguda gösterilmiştir. Bu gen noktalarının KS’ların patogenezinde yer alması ve innovatif tedavi seçeneklerinde hedef olarak kullanılmasının sağlanabilmesi için de, çoklu gen panelleri ile moleküler yöntemlerin kullanılacağı daha geniş vaka serileri ile yapılacak klinik çalışmalara ihtiyaç vardır.
Endometrial carcinosarcomas are very aggressive but rarely seen neoplasms that contain both high-grade carcinomatous and sarcomatous elements. The underlying pathogenesis and specific genetic changes are still not well known. In this study, we analyzed oncogenes which play a role in the pathogenesis of endometrial carcinosarcomas by NGS using tumor panel containing 12 genes and 1237 variant and compared with the clinicopathological data. The 12 patients who diagnosed as carcinosarcoma in Trakya University Faculty of Medicine, Department of Medical Pathology; were included in the study. Hematoxylin&Eosin sections were reviewed in light microscope. Histological subtyping was performed according to the current tumor classification (WHO). Existence of heterologous element, the depth of myometrial invasion, lymphovascular invasion and spread to other tissues/organs was evaluated. Detected mutation rates were 91.7% in EGFR, 41.7% in ERBB2, 25% in PDGFRA, 16.7% in KRAS/PIK3CA, and 8.3% in C-KIT genes, respectively. Endometrial carcinosarcomas exhibited similar heterogenity like endometrial carcinomas. Although there was no statistical significance between the detected gene mutations and the clinicopathological data, it was concluded that PDGFRA gene mutation may be related to the depth of myometrial invasion, lymphatic invasion and the presence of heterologous component. As a result, findings in our study about EGFR and ERBB2 variations, to explain the role of driver mutation in the pathogenesis of CSs and the potential of tyrosine kinase inhibitors to target these variations need more studies. PIK3CA and KRAS gene mutation, which are one of the most remarkable mutations in CSs, were shown in 2 cases in our study. In order to consider these gene points in the pathogenesis of CSs and to be used as a target for innovative treatment options, clinical studies with larger gene series and multiple gene panels are needed.
Endometrial carcinosarcomas are very aggressive but rarely seen neoplasms that contain both high-grade carcinomatous and sarcomatous elements. The underlying pathogenesis and specific genetic changes are still not well known. In this study, we analyzed oncogenes which play a role in the pathogenesis of endometrial carcinosarcomas by NGS using tumor panel containing 12 genes and 1237 variant and compared with the clinicopathological data. The 12 patients who diagnosed as carcinosarcoma in Trakya University Faculty of Medicine, Department of Medical Pathology; were included in the study. Hematoxylin&Eosin sections were reviewed in light microscope. Histological subtyping was performed according to the current tumor classification (WHO). Existence of heterologous element, the depth of myometrial invasion, lymphovascular invasion and spread to other tissues/organs was evaluated. Detected mutation rates were 91.7% in EGFR, 41.7% in ERBB2, 25% in PDGFRA, 16.7% in KRAS/PIK3CA, and 8.3% in C-KIT genes, respectively. Endometrial carcinosarcomas exhibited similar heterogenity like endometrial carcinomas. Although there was no statistical significance between the detected gene mutations and the clinicopathological data, it was concluded that PDGFRA gene mutation may be related to the depth of myometrial invasion, lymphatic invasion and the presence of heterologous component. As a result, findings in our study about EGFR and ERBB2 variations, to explain the role of driver mutation in the pathogenesis of CSs and the potential of tyrosine kinase inhibitors to target these variations need more studies. PIK3CA and KRAS gene mutation, which are one of the most remarkable mutations in CSs, were shown in 2 cases in our study. In order to consider these gene points in the pathogenesis of CSs and to be used as a target for innovative treatment options, clinical studies with larger gene series and multiple gene panels are needed.
Açıklama
Anahtar Kelimeler
Karsinosarkom, Moleküler Profil, Sekanslama, PIK3CA, EGFR, ERBB2, C-KIT, PDGFRA, KRAS, Mutasyon, Hedefe Yönelik Tedavi, Carcinosarcomas, Molecular Profiles, Sequencing, Mutation, Targeted Treatment
