1. Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer.
- Author
-
Post, Cathalijne C B, Stelloo, Ellen, Smit, Vincent T H B M, Ruano, Dina, Tops, Carli M, Vermij, Lisa, Rutten, Tessa A, Jürgenliemk-Schulz, Ina M, Lutgens, Ludy C H W, Jobsen, Jan J, Nout, Remi A, Crosbie, Emma J, Powell, Melanie E, Mileshkin, Linda, Leary, Alexandra, Bessette, Paul, Putter, Hein, Boer, Stephanie M de, Horeweg, Nanda, and Nielsen, Maartje
- Subjects
DIAGNOSIS of hereditary nonpolyposis colorectal cancer ,RESEARCH ,DNA ,HEREDITARY nonpolyposis colorectal cancer ,PROGNOSIS ,GENETIC disorders ,BRAIN tumors ,DNA methylation ,COLORECTAL cancer ,COMPARATIVE studies ,ENDOMETRIAL tumors ,DISEASE prevalence ,RESEARCH funding ,HEREDITARY cancer syndromes - Abstract
Background: Standard screening of endometrial cancer (EC) for Lynch syndrome (LS) is gaining traction; however, the prognostic impact of an underlying hereditary etiology is unknown. We established the prevalence, prognosis, and subsequent primary cancer incidence of patients with LS-associated EC in relation to sporadic mismatch repair deficient (MMRd)-EC in the large combined Post Operative Radiation Therapy in Endometrial Carcinoma-1, -2, and -3 trial cohort.Methods: After MMR-immunohistochemistry, MLH1-promoter methylation testing, and next-generation sequencing, tumors were classified into 3 groups according to the molecular cause of their MMRd-EC. Kaplan-Meier method, log-rank test, and Cox model were used for survival analysis. Competing risk analysis was used to estimate the subsequent cancer probability. All statistical tests were 2-sided.Results: Among the 1336 ECs, 410 (30.7%) were MMRd. A total of 380 (92.7%) were fully triaged: 275 (72.4%) were MLH1-hypermethylated MMRd-ECs; 36 (9.5%) LS MMRd-ECs, and 69 (18.2%) MMRd-ECs due to other causes. Limiting screening of EC patients to 60 years or younger or to 70 years or younger would have resulted in missing 18 (50.0%) and 6 (16.7%) LS diagnoses, respectively. Five-year recurrence-free survival was 91.7% (95% confidence interval [CI] = 83.1% to 100%; hazard ratio = 0.45, 95% CI = 0.16 to 1.24, P = .12) for LS, 95.5% (95% CI = 90.7% to 100%; hazard ratio = 0.17, 95% CI = 0.05 to 0.55, P = .003) for "other" vs 78.6% (95% CI = 73.8% to 83.7%) for MLH1-hypermethylated MMRd-EC. The probability of subsequent LS-associated cancer at 10 years was 11.6% (95% CI = 0.0% to 24.7%), 1.5% (95% CI = 0.0% to 4.3%), and 7.0% (95% CI = 3.0% to 10.9%) within the LS, "other," and MLH1-hypermethylated MMRd-EC groups, respectively.Conclusions: The LS prevalence in the Post Operative Radiation Therapy in Endometrial Carcinoma trial population was 2.8% and among MMRd-ECs was 9.5%. Patients with LS-associated ECs showed a trend towards better recurrence-free survival and higher risk for second cancers compared with patients with MLH1-hypermethylated MMRd-EC. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF