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Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer

 Young Shin Chung  ;  Ha Young Woo  ;  Jung-Yun Lee  ;  Eunhyang Park  ;  Eun Ji Nam  ;  Sunghoon Kim  ;  Sang Wun Kim  ;  Young Tae Kim 
 AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Vol.224(4) : 370.e1-370.e13, 2021-04 
Journal Title
Issue Date
Adult ; Antineoplastic Agents, Hormonal / therapeutic use ; Biomarkers / metabolism ; Biopsy ; DNA Mismatch Repair* ; DNA Polymerase II / genetics ; Disease Progression ; Endometrial Neoplasms / genetics ; Endometrial Neoplasms / metabolism ; Endometrial Neoplasms / therapy* ; Endometrium / pathology ; Female ; Fertility Preservation* ; Humans ; Hysterectomy / statistics & numerical data ; Intrauterine Devices, Medicated ; Medroxyprogesterone Acetate / therapeutic use ; Megestrol Acetate / therapeutic use ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local ; Prognosis ; Receptors, Progesterone / metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53 / genetics ; Young Adult
Proactive Molecular Risk Classifier for Endometrial Cancer ; endometrial cancer ; fertility-sparing ; hormone therapy ; mismatch repair ; molecular classification ; outcome ; progesterone
Background: Patients younger than 40 years usually present with early-stage endometrial cancer with favorable prognosis. However, such patients are usually in their childbearing age and may desire fertility-sparing options. The identification of biomarkers may improve the clinical outcomes in these patients and aid in fertility-sparing management; however, there has been no reports on biomarker analysis so far. Objective: This study aimed to evaluate the prognostic significance of Proactive Molecular Risk Classifier for Endometrial Cancer in the fertility-sparing management of endometrial cancer. Study design: A total of 57 endometrial biopsy specimens obtained before hormone therapy were evaluated, and patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer molecular subtypes (mismatch repair deficiency, DNA polymerase epsilon mutation, wild-type p53, and abnormal p53). The primary endpoint was the response rate after hormone therapy. The secondary endpoint was the recurrence rate after the complete response, hysterectomy rate owing to treatment failure, and upstaged diagnosis rate after hysterectomy. Results: Of 57 patients, 9 (15.8%) had mismatch repair deficiency, 2 (3.5%) had DNA polymerase epsilon mutation, 45 (78.9%) had wild-type p53, and 1 (1.8%) had abnormal p53. Overall, the complete response rate was 75.4% after hormone therapy. Patients with mismatch repair deficiency had a significantly lower complete response or partial response rate than those with wild-type p53 in terms of the best overall response (44.4% [95% confidence interval, 4.0-85.0] vs 82.2% [95% confidence interval, 71.0-94.0]; P=.018) and complete response rate at 6 months (11.1% [95% confidence interval, 0.2-37.0] vs 53.3% [95% confidence interval, 38.0-68.0]; P=.010). Among patients with mismatch repair deficiency, 4 underwent immediate hysterectomy because of treatment failure and 3 presented upstaged diagnosis after hysterectomy. Conclusion: The Proactive Molecular Risk Classifier for Endometrial Cancer molecular classification has prognostic significance in the fertility-sparing management of endometrial cancer, thereby enabling early stratification and risk assignment to direct care. Mismatch repair status could be used as a predictive biomarker for selecting patients who could benefit from hormone therapy. These findings need to be validated in larger studies.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Sung Hoon(김성훈) ORCID logo https://orcid.org/0000-0002-1645-7473
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
Nam, Eun Ji(남은지) ORCID logo https://orcid.org/0000-0003-0189-3560
Park, Eunhyang(박은향) ORCID logo https://orcid.org/0000-0003-2658-5054
Woo, Ha Young(우하영) ORCID logo https://orcid.org/0000-0002-3078-6484
Lee, Jung-Yun(이정윤) ORCID logo https://orcid.org/0000-0001-7948-1350
Chung, Young Shin(정영신)
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