Deficient mismatch repair in uterine adenocarcinoma: Frequency, clinicopathological correlations and prognostic implications

Ali Tümkaya; Kenan Serdar Dolapçıoğlu; Esin Doğan; Ahmet Beyazıt; Can Yazırlıoğlu

doi:10.19161/etd.1748970

TR EN

Uterin adenokarsinomda MMR protein ekspresyon kaybı: Sıklığı, klinikopatolojik korelasyonları ve prognostik etkileri

Öz

Amaç: Endometriyal kanser, dünya genelinde en sık görülen jinekolojik malignitedir. Cancer Genome Atlas (TGCA) moleküler sınıflandırması, mutasyon yükü ve kopya sayı değişikliklerine göre dört farklı moleküler alt tip tanımlamıştır. MMR protein ekspresyon kaybı (dMMR), geleneksel histopatolojik özelliklere kıyasla üstün prognostik bilgi sağlayan ve tedavi stratejilerini yönlendiren önemli moleküler belirteçlerden biridir. Bu çalışmanın amacı uterin adenokarsinomlu hastalarda dMMR sıklığını belirlemek ve bunun klinikopatolojik ve prognostik parametrelerle ilişkisini değerlendirmektir. Gereç ve Yöntem: Bu retrospektif çalışmada, Ocak 2019 ile Kasım 2024 tarihleri arasında uterin adenokarsinom/endometrioid karsinom tanısı alan elli hasta analiz edildi. İmmünohistokimyasal değerlendirme MSH1, MSH6, PMS2 ve MLH1 antikorları kullanılarak yapıldı. Hastalar, FIGO 2023 evreleme sistemine göre yeniden evrelendirildi. Bulgular: Yirmi hastada (%40) uyuşmayan onarım (MMR) proteini ekspresyonunda kayıp gözlendi. Çalışma grubunun ortalama yaşı 59,1±8,5 yıldı. İmmünohistokimyasal analiz, 3 hastada (%6) MSH2 kaybı, 4 hastada (%8) MSH6 kaybı, 13 hastada (%26) MLH1 kaybı ve 17 hastada (%34) PMS2 kaybı olduğunu gösterdi. MSI pozitifliği olan hastalar daha genç yaşta tanı aldı, daha yüksek lenfovasküler invazyon oranlarına sahipti ve lenf nodu metastazı açısından daha yüksek risk taşıdı (sırasıyla p:0,18; p:0,32; p:0,40). Sonuç: dMMR değerlendirmesi, endometrial kanserde değerli prognostik bilgi sağlar. Moleküler sınıflandırmanın, gelecekte adjuvan tedavi yaklaşımlarını yönlendirmede ve kişiye özel tedavi stratejileri geliştirmede kilit bir rol oynaması beklenmektedir.

Anahtar Kelimeler

Deficient mismatch repair in uterine adenocarcinoma: Frequency, clinicopathological correlations and prognostic implications

Abstract

Aim: Endometrial cancer is the most common gynecological malignancy worldwide. The Cancer Genome Atlas (TCGA) molecular classification system has identified four distinct molecular subtypes with mutation burden and copy number alterations. Deficient mismatch repair (dMMR) is an important molecular marker that provides superior prognostic information compared with traditional histopathological features and guides the treatment strategy. This study aimed is to determine the frequency of dMMR in patients with uterine adenocarcinoma and evaluate its relationship with clinicopathological and prognostic parameters. Materials and Methods: This retrospective study analyzed 50 patients diagnosed with uterine adenocarcinoma/endometrioid carcinoma between January 2019 and November 2024. Immunohistochemical evaluation was performed using antibodies against MSH1, MSH6, PMS2, and MLH1 proteins. The patients were restaged according to the Gynecology and Obstetrics International Federation of FIGO 2023 staging system. Results: Loss of mismatch repair (MMR) protein expression was observed in 20 patients (40%). The mean age of the participants was 59.18.5 years old. Immunohistochemical analysis revealed MSH2 loss in three patients (6%), MSH6 loss in four patients (8%), MLH1 loss in 13 patients (26%), and PMS2 loss in 17 patients (34%). Patients with dMMR were diagnosed at a younger age, had higher rates of lymphovascular invasion, and had a greater risk of metastasis (p:0,18; p:0,32; p:0,40 respectively). Conclusion: dMMR provides valuable prognostic information for endometrial cancer. Molecular classification is expected to play a pivotal role in guiding adjuvant treatment approaches and developing personalized therapeutic strategies in the future.

Keywords

Supporting Institution

This study was supported by the Mustafa Kemal University Scientific Research Projects Unit under Project Number 25.TU.001

Project Number

25.TU.001

Thanks

This study was supported by the Mustafa Kemal University Scientific Research Projects Unit under Project Number 25.TU.001 Conflict of Interest: Authors declared no conflict of interest

References

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Details

Primary Language

English

Subjects

Gynecologic Oncology Surgery , Obstetrics and Gynaecology

Journal Section

Research Article

Authors

Ali Tümkaya
0009-0001-3215-2338
Türkiye

Kenan Serdar Dolapçıoğlu
0000-0002-2296-9037
Türkiye

Esin Doğan
0000-0002-5242-2753
Türkiye

Ahmet Beyazıt ^*
0000-0001-5517-9624
Türkiye

Can Yazırlıoğlu
0000-0002-7843-4357
Türkiye

Publication Date

March 9, 2026

Submission Date

July 23, 2025

Acceptance Date

October 21, 2025

Published in Issue

Year 2026 Volume: 65 Number: 1

DOI

https://doi.org/10.19161/etd.1748970

IZ

https://izlik.org/JA83DG26FA

Cite

RIS / Bibtex

Vancouver

1.Ali Tümkaya, Kenan Serdar Dolapçıoğlu, Esin Doğan, Ahmet Beyazıt, Can Yazırlıoğlu. Deficient mismatch repair in uterine adenocarcinoma: Frequency, clinicopathological correlations and prognostic implications. EJM. 2026 Mar. 1;65(1):33-9. doi:10.19161/etd.1748970