Endometrium Kanserinde Moleküler Onkolojinin Yeri
Özet
Endometrium kanserinde Dünya Sağlık Örgütü (WHO) ve The Cancer Genome Atlas (TCGA) tarafından önerilen yeni moleküler sınıflandırma sistemleri, geleneksel yöntemlerin yetersiz kaldığı alanları tamamlamaktadır. Geleneksel histomorfolojik sistem tümörleri tip 1 ve tip 2 olarak ikiye ayırırken, bazı hastaların yönetimi bu sınırlı kategorizasyon nedeniyle karmaşık hale gelmektedir. 2013 yılında TCGA, genomik ve proteomik analizlerle endometrium kanserini dört farklı moleküler alt tipe ayırmıştır: Ultramutasyona uğramış (POLE mut), Hipermutasyona uğramış (MMRd), Kopya sayısı düşük (NSMP/p53wt) ve Kopya sayısı yüksek (p53abn). Bu alt tipler, hastalarda farklı prognostik sonuçlar ve klinik özellikler göstermektedir. POLE mut grubu en iyi prognoza sahipken, p53abn grubu en agresif seyri ve en kötü prognozu sergilemektedir. 2020 ESGO/ESTRO/ESP kılavuzları, bu moleküler alt tipleri risk gruplarına entegre ederek tedavi yönetimini ve adjuvan tedavi (radyoterapi, kemoterapi) ihtiyaçlarını yeniden şekillendirmiştir. Moleküler profilleme, özellikle erken evre hastalıklarda ek tedavi gereksinimini netleştirmekte ve hastaların yanlış sınıflandırılmasını önlemektedir. Histolojik olarak ise endometroiid, seröz, berrak hücreli, karma, undiferansiye karsinom ve karsinosarkom gibi tiplerin bu moleküler alt tiplerle olan ilişkisi ve genetik heterojenliği vurgulanmaktadır.
New molecular classification systems recommended by the World Health Organization (WHO) and The Cancer Genome Atlas (TCGA) in endometrial cancer complement the areas where traditional methods fall short. While the traditional histomorphological system divides tumors into type 1 and type 2, the management of some patients becomes complicated due to this limited categorization. In 2013, the TCGA classified endometrial cancer into four distinct molecular subtypes through genomic and proteomic analyses: Ultramutated (POLE mut), Hypermutated (MMRd), Copy-number low (NSMP/p53wt), and Copy-number high (p53abn). These subtypes demonstrate different prognostic outcomes and clinicopathological characteristics in patients. The POLE mut group exhibits the most favorable prognosis, whereas the p53abn group shows the most aggressive behavior and the poorest prognosis. The 2020 ESGO/ESTRO/ESP guidelines have reshaped treatment management and adjuvant therapy requirements (radiotherapy, chemotherapy) by integrating these molecular subtypes into risk groups. Molecular profiling clarifies the need for additional therapy, especially in early-stage disease, and prevents the misclassification of patients. Histologically, the relationship of types such as endometrioid, serous, clear cell, mixed, undifferentiated carcinoma, and carcinosarcoma with these molecular subtypes and their genetic heterogeneity is emphasized.
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