Clinicopathologic characteristics and outcomes of endometrial Cancer patients with mismatch repair deficiency in the era of universal Lynch syndrome screening.

Carr, Caitlin; Son, Jessica; Yao, Meng; Priyadarshini, Anju; Marquard, Jessica; Vargas, Roberto; Michener, Chad; AlHilli, Mariam M

Carr, Caitlin; Son, Jessica; Yao, Meng; Priyadarshini, Anju; Marquard, Jessica; Vargas, Roberto; Michener, Chad; AlHilli, Mariam M.

Afiliación

Carr C; Department of Obstetrics and Gynecology, Divison of Gynecologic Oncology, Icahan School of Medicine at Mount Sinai, New York, United States of America.
Son J; Department of Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, United States of America.
Yao M; Department of Quantitative Health Sciences, Seciton of Biostatistics, Cleveland Clinic, Cleveland, OH, United States of America.
Priyadarshini A; Department of Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, United States of America.
Marquard J; Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, United States of America.
Vargas R; Department of Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, United States of America.
Michener C; Department of Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, United States of America.
AlHilli MM; Department of Obstetrics and Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, United States of America. Electronic address: alhillm@ccf.org.

Gynecol Oncol ; 159(3): 712-720, 2020 12.

Article en En | MEDLINE | ID: mdl-33046272

RESUMEN

OBJECTIVE: To evaluate clinicopathologic characteristics and survival impact associated with mismatch repair (MMR) deficient subgroups of endometrial cancer (EC) in patients undergoing universal screening for Lynch Syndrome. METHODS: A retrospective cohort study using a prospectively maintained gynecologic oncology registry of patients who underwent surgery for EC was conducted. All pathology specimens underwent tumor testing using immunohistochemistry for MMR deficiency with reflex MLH1 promotor methylation testing. Tumors were classified as MMR-I (intact MMR expression), MMR-DM (MMR deficient due to MLH1 methylation), and MMR-DU (MMR deficient without MLH1 methylation). Univariate and multivariate analysis performed to determine factors associated with MMR-DM. Progression-free survival (PFS) and overall survival (OS) analyzed by stage and endometrioid subgroup. RESULTS: From 2012 to 2016, 1018 EC patients were identified and screened. Overall, 71.6% were classified as MMR-I, 23.8% MMR-DM, and 4.6% MMR-DU. In comparison to MMR-DU, MMR-DM tumors were associated with older age, postmenopausal status, lymphovascular space invasion, and pure endometrioid histology. Compared to MMR-I, MMR-DM tumors were associated with older age, endometrioid histology, lymphovascular space invasion, and higher grade on multivariable analysis. There was no difference in PFS and OS between the three groups overall. In patients with endometrioid EC, MMR-DM tumors were associated with lower PFS vs. MMR-I (HR:2.51, CI:1.54, 4.10, P < 0.001). This effect persisted for stage I/II endometrioid EC (HR 2.66, CI:1.34, 5.26 p = 0.005). No difference in PFS or OS was noted among stage III/IV endometrioid tumors. CONCLUSION: MMR deficiency is associated with adverse prognostic factors and worse PFS among endometrioid tumors, particularly in early stage EC. MMR testing outside of LS screening has prognostic value, warranting consideration for inclusion as a biomarker in prospective clinical trials.

Asunto(s)

Carcinoma Endometrioide/mortalidad; Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico; Reparación de la Incompatibilidad de ADN; Detección Precoz del Cáncer/estadística & datos numéricos; Neoplasias Endometriales/mortalidad; Factores de Edad; Anciano; Carcinoma Endometrioide/diagnóstico; Carcinoma Endometrioide/genética; Carcinoma Endometrioide/cirugía; Neoplasias Colorrectales Hereditarias sin Poliposis/genética; Metilación de ADN; Detección Precoz del Cáncer/métodos; Neoplasias Endometriales/diagnóstico; Neoplasias Endometriales/genética; Neoplasias Endometriales/cirugía; Endometrio/patología; Endometrio/cirugía; Femenino; Humanos; Histerectomía; Persona de Mediana Edad; Homólogo 1 de la Proteína MutL/deficiencia; Homólogo 1 de la Proteína MutL/genética; Mutación; Clasificación del Tumor; Invasividad Neoplásica/genética; Estadificación de Neoplasias; Pronóstico; Supervivencia sin Progresión; Regiones Promotoras Genéticas/genética; Estudios Prospectivos; Sistema de Registros/estadística & datos numéricos; Estudios Retrospectivos; Factores de Riesgo

Palabras clave

Endometrial cancer; Endometrioid endometrial cancer; Mismatch repair deficiency

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales Hereditarias sin Poliposis / Neoplasias Endometriales / Carcinoma Endometrioide / Reparación de la Incompatibilidad de ADN / Detección Precoz del Cáncer Tipo de estudio: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Gynecol Oncol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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