Journal article
The prognostic impact of MLH1 promoter hypermethylation in stage I-II endometrial cancer treated with adjuvant radiotherapy: a multi-institutional retrospective study: MLH1ph status in stage I-II endometrial cancer
International journal of radiation oncology, biology, physics, v 123(2)
14 May 2025
PMID: 40379143
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To assess the impact of MLH1 promoter hypermethylation (MLH1ph) on prognosis and define the patterns of recurrence in stage I-II endometroid endometrial cancer (EEC) treated with adjuvant radiotherapy.
In a retrospective, IRB-approved, multi-institutional cohort study, 814 patients with stage I-II EEC with known mismatch repair (MMR) status were included. Tumors with MSH2, MSH6, MLH1 or PMS2 mutations were classified as somatic dMMR (sdMMR), while tumors with epigenetic silencing of the MLH1 promoter were classified as MLH1ph. Recurrence-free survival (RFS) was calculated by the Kaplan Meier method. Univariate and multivariate analyses (UVA/MVA) were performed via Cox proportional hazards. Statistical analyses were conducted using SPSS version 27.
The median age at diagnosis was 65 (IQR 58-71) and most patients had grade 2-3 disease (59.2%), ≥50% myometrial invasion (56.0%) and absence of lymphovascular space invasion (58%). Vaginal brachytherapy was delivered to 643 (78.1%) patients, while 180 (21.9%) patients received external beam radiation (EBRT) ± VBT. MMR was proficient in 550 (67.6%) patients and deficient in 264 (32.4%) patients. Of the patients with dMMR, most patients harbored MLH1ph (n=171, 66%), while 93 patients (35.2%) had somatic dMMR. Tumor size ≥ 3.8cm (HR 2.2, p=0.003), MMR deficient vs proficient (HR 2.7, p<0.001) and EBRT±VBT vs VBT alone (HR 1.9, p=0.032) were associated with decreased RFS on MVA. On subgroup analysis including patients with dMMR only, patients with MLH1ph had worse RFS compared to patients with sdMMR (HR 1.9 (95% CI1.1-3.6), p=0.025). Distant recurrence was the most common recurrence site, regardless of MMR status. Patients with MLH1ph had significantly higher proportion of vaginal (5% vs 0% vs 2%) and pelvic (5.3% vs 3.2% vs 0.5%) recurrences compared with sdMMR and pMMR, respectively (p=0.038).
Patients with MLH1ph had worse RFS, which may be attributed in part to a higher proportion of locoregional recurrences compared to the pMMR and sdMMR patients.
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Details
- Title
- The prognostic impact of MLH1 promoter hypermethylation in stage I-II endometrial cancer treated with adjuvant radiotherapy: a multi-institutional retrospective study: MLH1ph status in stage I-II endometrial cancer
- Creators
- Zohaib K Sherwani - Rutgers, The State University of New JerseyShari Damast - Yale UniversityEmma C Fields - Virginia Commonwealth UniversitySushil Beriwal - Allegheny Health NetworkZachary D Horne - Allegheny Health NetworkElizabeth A Kidd - Stanford UniversityEric W Leung - Sunnybrook Health Science CentreNeil K Taunk - University of PennsylvaniaJunzo Chino - Duke Medical CenterAndrea L Russo - Massachusetts General HospitalMichael Dyer - Harvard UniversityKevin V Albuquerque - The University of Texas Southwestern Medical CenterLara Hathout - Rutgers, The State University of New Jersey
- Publication Details
- International journal of radiation oncology, biology, physics, v 123(2)
- Publisher
- Elsevier
- Number of pages
- 8
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Radiation Oncology (and Nuclear Medicine)
- Web of Science ID
- WOS:001570548600012
- Scopus ID
- 2-s2.0-105007061149
- Other Identifier
- 991022053728804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology
- Radiology, Nuclear Medicine & Medical Imaging