Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer.

Autor:	Post CCB; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands., Stelloo E; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Smit VTHBM; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Ruano D; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Tops CM; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands., Vermij L; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Rutten TA; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Jürgenliemk-Schulz IM; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands., Lutgens LCHW; Department of Radiation Oncology, MAASTRO Clinic, Maastricht, the Netherlands., Jobsen JJ; Department of Radiation Oncology, Medical Spectrum Twente, Enschede, the Netherlands., Nout RA; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands., Crosbie EJ; Division of Cancer Sciences, University of Manchester, St Mary's Hospital, Manchester, UK.; Department of Obstetrics and Gynaecology, Manchester University NHS Foundation Trust, Manchester, UK., Powell ME; Department of Clinical Oncology, Barts Health NHS Trust, London, UK., Mileshkin L; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Leary A; Department of Medical Oncology, Gustave Roussy Cancer Center-INSERM U981, Université Paris Saclay, Villejuif, France., Bessette P; Department of Obstetrics and Gynecology, University of Sherbrooke, Sherbrooke, Quebec, Canada., Putter H; Department of Biostatistics, Leiden University Medical Center, Leiden, the Netherlands., de Boer SM; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands., Horeweg N; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands., Nielsen M; Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands., Wezel TV; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Bosse T; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands., Creutzberg CL; Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2021 Sep 04; Vol. 113 (9), pp. 1212-1220.
DOI:	10.1093/jnci/djab029
Abstrakt:	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. (© The Author(s) 2021. Published by Oxford University Press.)
Databáze:	MEDLINE
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