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Prognostic Significance of Mismatch Repair Protein Expression and Its Association with Clinical Outcomes in Endometrial Cancer

Year 2025, Volume: 16 Issue: 2, 203 - 211, 18.08.2025
https://doi.org/10.22312/sdusbed.1681755

Abstract

Objective: This study aimed to evaluate the expression of mismatch repair (MMR) proteins in patients with endometrial cancer (EC), compare the findings with clinicopathological data, and investigate their prognostic implications. Materials and Methods: A total of 116 patients diagnosed with EC via endometrial biopsy or resection at Isparta City Hospital between March 1, 2017, and January 1, 2023, were included. Immunohistochemical analysis was performed to assess the expression of MMR proteins (MLH1, PMS2, MSH2, MSH6). Patients were classified as microsatellite stable (MSS) or microsatellite instable (MSI) based on MMR protein expression, and correlations with clinicopathological features and survival outcomes were analyzed. Results: Among the patients, 83.6% were classified as MSS and 16.4% as MSI. MSI was more frequently observed in patients under 60 years of age, with endometrioid type, low tumor grade, and hormone receptor positivity; however, these associations were not statistically significant. Estrogen receptor (ER) positivity, p53 mutation status, and microsatellite instability (MSI) were significant predictors of survival in endometrial cancer. The median overall survival (OS) was 31 months in the MSS group and 52 months in the MSI group, indicating a statistically significant difference (p = 0.002). Conclusion: MMR deficiency and MSI status are of prognostic significance in EC. MSI positivity is associated with longer survival and increased sensitivity to immunotherapy, highlighting its value as a clinically meaningful biomarker. Molecular classification can provide guidance for personalized treatment strategies.

Ethical Statement

This study was approved by the Ethics Committee of Süleyman Demirel University Medical Faculty (dated 12.01.2023, number: 9).

References

  • 1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May 4;74(3):229–63. doi.org/10.3322/caac.21834.
  • 2. Peeri NC, Bertrand KA, Na R, De Vivo I, Setiawan VW, Seshan VE, et al. Understanding risk factors for endometrial cancer in young women. JNCI: Journal of the National Cancer Institute. 2025 Jan 1;117(1):76–88. doi.org/10.1093/jnci/djae210 .
  • 3. Baker-Rand H, Kitson SJ. Recent Advances in Endometrial Cancer Prevention, Early Diagnosis and Treatment. Cancers (Basel). 2024 Mar 1;16(5):1028. doi.org/10.3390/cancers16051028
  • 4. Jo A, Shoji T, Otsuka H, Abe M, Tatsuki S, Chiba Y, et al. Treatment strategies for advanced and recurrent endometrial cancer using immune checkpoint inhibitors. Int J Clin Oncol. 2025 Feb 15;30(2):229–40. doi.org/10.1007/s10147-024-02689-8.
  • 5. Anca-Stanciu MB, Manu A, Olinca MV, Coroleucă C, Comandașu DE, Coroleuca CA, et al. Comprehensive Review of Endometrial Cancer: New Molecular and FIGO Classification and Recent Treatment Changes. J Clin Med. 2025 Feb 19;14(4):1385. doi.org/10.3390/jcm14041385.
  • 6. Lee HJ, Lee B. Impacts of Postoperative Adjuvant Therapies on the Survival of Women with High-Risk Early-Stage Endometrial Cancer: A Cohort Study. Cancers (Basel). 2025 Jan 8;17(2):187. 10.3390/cancers17020187
  • 7. Banerjee S, Hasson SP. Top advances of the year: Immunotherapy in endometrial cancer. Cancer. 2024 Sep 15;130(18):3082–6. doi.org/10.1002/cncr.35417.
  • 8. Addante F, d’Amati A, Santoro A, Angelico G, Inzani F, Arciuolo D, et al. Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Endometrial Cancer: A Review on Immunohistochemistry Staining Patterns and Clinical Implications. Int J Mol Sci. 2024 Jan 15;25(2):1056. doi.org/10.3390/ijms25021056.
  • 9. Ma J, Lin J, Lin X, Ren Y, Liu D, Tang S, et al. Assessment of Immune Status in Patients with Mismatch Repair Deficiency Endometrial Cancer. J Inflamm Res. 2024 Apr;Volume 17:2039–50. doi.org/10.2147/JIR.S453337
  • 10. Ambrosini M, Manca P, Nasca V, Sciortino C, Ghelardi F, Seligmann JF, et al. Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers. Nat Rev Clin Oncol. 2025 Apr 3; doi.org/10.1038/s41571-025-01015-z.
  • 11. Slomovitz BM, Cibula D, Lv W, Ortaç F, Hietanen S, Backes F, et al. Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors. Journal of Clinical Oncology. 2025 Jan 20;43(3):251–9. doi.org/10.1200/JCO-24-01887.
  • 12. Walsh CS, Hacker KE, Secord AA, DeLair DF, McCourt C, Urban R. Molecular testing for endometrial cancer: An SGO clinical practice statement. Gynecol Oncol. 2023 Jan;168:48–55. doi.org/10.1016/j.ygyno.2022.10.024
  • 13. Di Dio C, Bogani G, Di Donato V, Cuccu I, Muzii L, Musacchio L, et al. The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma. Gynecol Oncol. 2023 Feb;169:27–33. doi.org/10.1016/j.ygyno.2022.11.031.
  • 14. Casey L, Singh N. POLE, MMR, and MSI Testing in Endometrial Cancer: Proceedings of the ISGyP Companion Society Session at the USCAP 2020 Annual Meeting. International Journal of Gynecological Pathology. 2021 Jan;40(1):5–16. doi.org/10.1097/PGP.0000000000000710.
  • 15. Yeh JT, Peng HP, Hung FH, Hung CF, Hsieh LL, Yang AS, et al. Mismatch Repair (MMR) Gene Mutation Carriers Have Favorable Outcome in Colorectal and Endometrial Cancer: A Prospective Cohort Study. Cancers (Basel). 2024 Jun 26;16(13):2342. doi.org/10.3390/cancers16132342.
  • 16. Nádorvári ML, Kenessey I, Kiss A, Barbai T, Kulka J, Rásó E, et al. Comparison of standard mismatch repair deficiency and microsatellite instability tests in a large cancer series. J Transl Med. 2024 Feb 13;22(1):150. doi.org/10.1186/s12967-024-04960-y.
  • 17. Ali-Fehmi R, Krause HB, Morris RT, Wallbillich JJ, Corey L, Bandyopadhyay S, et al. Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors. JCO Precis Oncol. 2024 Oct;(8). doi.org/10.1200/PO.23.00648.
  • 18. Zhao S, Chen L, Zang Y, Liu W, Liu S, Teng F, et al. Endometrial cancer in Lynch syndrome. Int J Cancer. 2022 Jan 9;150(1):7–17. doi.org/10.1002/ijc.33763.
  • 19. Rafaniello-Raviele P, Betella I, Rappa A, Vacirca D, Tolva G, Guerrieri-Gonzaga A, et al. Microsatellite instability evaluation: which test to use for endometrial cancer? J Clin Pathol. 2023 Jan;76(1):29–33. doi.org/10.1136/jclinpath-2021-207723.

Endometrial Kanserde Mismatch Repair Protein Ekspresyonunun Prognostik Önemi ve Klinik Sonuçlarla İlişkisi

Year 2025, Volume: 16 Issue: 2, 203 - 211, 18.08.2025
https://doi.org/10.22312/sdusbed.1681755

Abstract

Amaç: Bu çalışmada, endometrial kanser (EK) hastalarında MMR (Mismatch Repair) protein ekspresyonunu değerlendirmek, bu bulguları klinikopatolojik verilerle karşılaştırmak ve prognostik etkilerini incelemek amaçlanmıştır. Gereç ve Yöntem: Çalışmaya, 1 Mart 2017 - 1 Ocak 2023 tarihleri arasında Isparta Şehir Hastanesi’nde endometrial biyopsi veya rezeksiyon ile EK tanısı alan 116 hasta dahil edilmiştir. MMR protein ekspresyonu (MLH1, PMS2, MSH2, MSH6) immünohistokimyasal yöntemle değerlendirilmiştir. MSS (mikrosatellit stabil) ve MSI (mikrosatellit instabil) olarak sınıflandırılan hastalar klinikopatolojik özellikler ve sağkalım açısından analiz edilmiştir. Bulgular: Hastaların %83.6’sı MSS, %16.4’ü MSI olarak saptanmıştır. MSI olguları daha çok <60 yaş, endometrioid tip, düşük tümör derecesi ve hormon reseptör pozitifliği ile ilişkilidir; ancak bu ilişkiler istatistiksel anlamlılık göstermemiştir. Endometrial kanserde östrojen reseptörü (ER) pozitifliği, p53 mutasyon durumu ve mikrosatellit instabilitesi (MSI), sağkalımın anlamlı belirleyicileri olarak saptanmıştır. Medyan genel sağkalım (OS), MSS grubunda 31 ay iken, MSI grubunda 52 ay olarak bulunmuş ve bu fark istatistiksel olarak anlamlıdır (p=0.002). Sonuç: MMR yetersizliği ve MSI durumu, EK’de prognostik öneme sahiptir. MSI pozitifliği, daha uzun sağkalım ve immünoterapiye duyarlılık açısından klinik olarak anlamlı bir biyobelirteçtir. Moleküler sınıflandırma, kişiselleştirilmiş tedavi stratejileri açısından yol gösterici olabilir.

References

  • 1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May 4;74(3):229–63. doi.org/10.3322/caac.21834.
  • 2. Peeri NC, Bertrand KA, Na R, De Vivo I, Setiawan VW, Seshan VE, et al. Understanding risk factors for endometrial cancer in young women. JNCI: Journal of the National Cancer Institute. 2025 Jan 1;117(1):76–88. doi.org/10.1093/jnci/djae210 .
  • 3. Baker-Rand H, Kitson SJ. Recent Advances in Endometrial Cancer Prevention, Early Diagnosis and Treatment. Cancers (Basel). 2024 Mar 1;16(5):1028. doi.org/10.3390/cancers16051028
  • 4. Jo A, Shoji T, Otsuka H, Abe M, Tatsuki S, Chiba Y, et al. Treatment strategies for advanced and recurrent endometrial cancer using immune checkpoint inhibitors. Int J Clin Oncol. 2025 Feb 15;30(2):229–40. doi.org/10.1007/s10147-024-02689-8.
  • 5. Anca-Stanciu MB, Manu A, Olinca MV, Coroleucă C, Comandașu DE, Coroleuca CA, et al. Comprehensive Review of Endometrial Cancer: New Molecular and FIGO Classification and Recent Treatment Changes. J Clin Med. 2025 Feb 19;14(4):1385. doi.org/10.3390/jcm14041385.
  • 6. Lee HJ, Lee B. Impacts of Postoperative Adjuvant Therapies on the Survival of Women with High-Risk Early-Stage Endometrial Cancer: A Cohort Study. Cancers (Basel). 2025 Jan 8;17(2):187. 10.3390/cancers17020187
  • 7. Banerjee S, Hasson SP. Top advances of the year: Immunotherapy in endometrial cancer. Cancer. 2024 Sep 15;130(18):3082–6. doi.org/10.1002/cncr.35417.
  • 8. Addante F, d’Amati A, Santoro A, Angelico G, Inzani F, Arciuolo D, et al. Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Endometrial Cancer: A Review on Immunohistochemistry Staining Patterns and Clinical Implications. Int J Mol Sci. 2024 Jan 15;25(2):1056. doi.org/10.3390/ijms25021056.
  • 9. Ma J, Lin J, Lin X, Ren Y, Liu D, Tang S, et al. Assessment of Immune Status in Patients with Mismatch Repair Deficiency Endometrial Cancer. J Inflamm Res. 2024 Apr;Volume 17:2039–50. doi.org/10.2147/JIR.S453337
  • 10. Ambrosini M, Manca P, Nasca V, Sciortino C, Ghelardi F, Seligmann JF, et al. Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers. Nat Rev Clin Oncol. 2025 Apr 3; doi.org/10.1038/s41571-025-01015-z.
  • 11. Slomovitz BM, Cibula D, Lv W, Ortaç F, Hietanen S, Backes F, et al. Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors. Journal of Clinical Oncology. 2025 Jan 20;43(3):251–9. doi.org/10.1200/JCO-24-01887.
  • 12. Walsh CS, Hacker KE, Secord AA, DeLair DF, McCourt C, Urban R. Molecular testing for endometrial cancer: An SGO clinical practice statement. Gynecol Oncol. 2023 Jan;168:48–55. doi.org/10.1016/j.ygyno.2022.10.024
  • 13. Di Dio C, Bogani G, Di Donato V, Cuccu I, Muzii L, Musacchio L, et al. The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma. Gynecol Oncol. 2023 Feb;169:27–33. doi.org/10.1016/j.ygyno.2022.11.031.
  • 14. Casey L, Singh N. POLE, MMR, and MSI Testing in Endometrial Cancer: Proceedings of the ISGyP Companion Society Session at the USCAP 2020 Annual Meeting. International Journal of Gynecological Pathology. 2021 Jan;40(1):5–16. doi.org/10.1097/PGP.0000000000000710.
  • 15. Yeh JT, Peng HP, Hung FH, Hung CF, Hsieh LL, Yang AS, et al. Mismatch Repair (MMR) Gene Mutation Carriers Have Favorable Outcome in Colorectal and Endometrial Cancer: A Prospective Cohort Study. Cancers (Basel). 2024 Jun 26;16(13):2342. doi.org/10.3390/cancers16132342.
  • 16. Nádorvári ML, Kenessey I, Kiss A, Barbai T, Kulka J, Rásó E, et al. Comparison of standard mismatch repair deficiency and microsatellite instability tests in a large cancer series. J Transl Med. 2024 Feb 13;22(1):150. doi.org/10.1186/s12967-024-04960-y.
  • 17. Ali-Fehmi R, Krause HB, Morris RT, Wallbillich JJ, Corey L, Bandyopadhyay S, et al. Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors. JCO Precis Oncol. 2024 Oct;(8). doi.org/10.1200/PO.23.00648.
  • 18. Zhao S, Chen L, Zang Y, Liu W, Liu S, Teng F, et al. Endometrial cancer in Lynch syndrome. Int J Cancer. 2022 Jan 9;150(1):7–17. doi.org/10.1002/ijc.33763.
  • 19. Rafaniello-Raviele P, Betella I, Rappa A, Vacirca D, Tolva G, Guerrieri-Gonzaga A, et al. Microsatellite instability evaluation: which test to use for endometrial cancer? J Clin Pathol. 2023 Jan;76(1):29–33. doi.org/10.1136/jclinpath-2021-207723.
There are 19 citations in total.

Details

Primary Language English
Subjects Pathology
Journal Section Araştırma Articlesi
Authors

Ramazan Oğuz Yüceer 0000-0002-9418-8862

Mehmet Kıran 0000-0003-3292-2213

Serhan Can İscan 0000-0002-3824-5818

Publication Date August 18, 2025
Submission Date April 22, 2025
Acceptance Date July 4, 2025
Published in Issue Year 2025 Volume: 16 Issue: 2

Cite

Vancouver Yüceer RO, Kıran M, İscan SC. Prognostic Significance of Mismatch Repair Protein Expression and Its Association with Clinical Outcomes in Endometrial Cancer. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2025;16(2):203-11.

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