Molecular classification and clinicopathological features of grade 3 endometrioid endometrial carcinoma

Year 2025, Volume: 50 Issue: 3, 890 - 898, 30.09.2025

Ümran Küçükgöz Güleç , Emine Kılıç Bağır , Semra Paydaş , Ayşe Daş Çerçi Emine Küçükbingöz , Derya Gümürdülü , Ersel Güleç , Ghanim Khatib Mehmet Ali Vardar

https://doi.org/10.17826/cumj.1720831

Abstract

Purpose: This study investigates the molecular characteristics of grade 3 endometrioid endometrial carcinoma (EC) through immunohistochemical analysis of mismatch repair (MMR) proteins and p53, correlating molecular subtypes with clinicopathological features and survival outcomes.
Materials and Methods: We retrospectively analyzed 33 patients with surgically staged grade 3 endometrioid EC. Immunohistochemical analysis was performed to assess MMR protein (MLH1, MSH2, MSH6, PMS2) and p53 expression. Cases were classified into MMR-deficient (MMRd), p53 wild-type (p53wt), and p53 abnormal (p53abn) molecular subtypes. A comparative analysis was conducted on clinicopathological characteristics and survival outcomes across molecular subgroups.
Results: The molecular subtype distribution was: MMRd (36.4%), p53abn (15.2%), and p53wt (48.5%). Clinicopathological features, including age, stage, myometrial invasion, lymph node metastasis, and lymphovascular space invasion did not significantly differ across molecular subgroups. The p53abn group showed a non-significant trend toward reduced overall survival while disease-free survival was similar among the groups.
Conclusion: Routine IHC assessment is a practical approach to identify molecular subtypes, particularly MMRd tumors that may benefit from immunotherapy, and p53abn tumors that may warrant intensified treatment strategies.

Keywords

Endometrial Carcinoma , Molecular Classification , Grade 3 , Immunohistochemistry

Ethical Statement

The study received ethical approval by the faculty's Local Ethics Committee. This study adhered to the guidelines set forth by the Declaration of Helsinki. The Non-Interventional Clinical Research Ethics Committee at Cukurova University, Faculty of Medicine, granted approval (IRB number: 108, Date: February 12, 2021).

Supporting Institution

This study was supported by the coordination unit of Scientific Research Projects (BAP- TDK-2021-13714) of Çukurova University.

Project Number

BAP- TDK-2021-13714

Thanks

We thanks to Scientific Research Projects of CUkurova University and İlker Ünal for statictical analysis of the study.

Grade 3 endometrioid tip endometrial karsinomun moleküler sınıflaması ve klinik-patolojik özellikleri

Abstract

Amaç: Bu çalışmada, mismatch repair (MMR) proteinleri ve p53'ün immünohistokimyasal analizi yoluyla grade 3 endometrioid endometrial karsinom (EC) moleküler özelliklerinin belirlenmesi, moleküler alt tiplerin klinik-patolojik özellikler ve sağkalım sonuçları ile ilişkilendirilmesi amaçlanmıştır.
Gereç ve Yöntem: Cerrahi olarak evrelendirilmiş grade 3 endometrioid EC'li 33 hasta retrospektif olarak analiz edildi. MMR proteini (MLH1, MSH2, MSH6, PMS2) ve p53 ekspresyonunu değerlendirmek için immünohistokimyasal analiz yapıldı. Vakalar MMR eksikliği olan (MMRd), p53 wild tip (p53wt) ve p53 mutant (p53abn) moleküler alt tipler olarak sınıflandırıldı. Moleküler alt gruplar arasında klinik-patolojik özellikler ve sağ kalım sonuçları üzerine karşılaştırmalı bir analiz yapılmıştır.
Bulgular: Moleküler alt tip dağılımı şöyleydi: MMRd (%36.4), p53abn (%15.2) ve p53wt (%48.5). Yaş, evre, myometrial invazyon, lenf nodu metastazı ve lenfovasküler alan invazyonu gibi klinik-patolojik özellikler moleküler alt gruplar arasında anlamlı farklılık göstermedi. P53abn grubu genel sağkalımda azalma yönünde anlamlı olmayan bir eğilim gösterirken, hastalıksız sağkalım gruplar arasında benzerdi.
Sonuç: Rutin IHC değerlendirme, özellikle immünoterapiden fayda sağlayabilecek MMRd tümörleri ve yoğunlaştırılmış tedavi stratejileri gerektirebilecek p53abn tümörleri başta olmak üzere moleküler alt tipleri tanımlamak için pratik bir yaklaşımdır.

Keywords

Endometrial Karsinom , Grade 3 , Moleküler Sınıflandırma , İmmünohistokimya

Project Number

BAP- TDK-2021-13714

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