title: Genetic analysis of uterine aspirates improves the diagnostic value and captures the intra-tumor heterogeneity of endometrial cancers.
abstract: Endometrial cancer is the most common cancer of the female genital tract in developed countries. Although the majority of endometrial cancers are diagnosed at early stages and the 5-year overall survival is around 80%, early detection of these tumors is crucial to improve the survival of patients given that the advanced tumors are associated with a poor outcome. Furthermore, correct assessment of the pre-clinical diagnosis is decisive to guide the surgical treatment and management of the patient. In this sense, the potential of targeted genetic sequencing of uterine aspirates has been assessed as a pre-operative tool to obtain reliable information regarding the mutational profile of a given tumor, even in samples that are not histologically classifiable. A total of 83 paired samples were sequenced (uterine aspirates and hysterectomy specimens), including 62 endometrioid and non-endometrioid tumors, 10 cases of atypical hyperplasia and 11 non-cancerous endometrial disorders. Even though diagnosing endometrial cancer based exclusively on genetic alterations is currently unfeasible, mutations were mainly found in uterine aspirates from malignant disorders, suggesting its potential in the near future for supporting the standard histologic diagnosis. Moreover, this approach provides the first evidence of the high intra-tumor genetic heterogeneity associated with endometrial cancer, evident when multiple regions of tumors are analyzed from an individual hysterectomy. Notably, the genetic analysis of uterine aspirates captures this heterogeneity, solving the potential problem of incomplete genetic characterization when a single tumor biopsy is analyzed.
authors: Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.|MD Anderson International Foundation, Madrid, Spain.
authors: Alba
authors: 0000-0001-9148-3965
authors: A
authors: Mota
authors: Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
authors: Eva
authors: E
authors: Colás
authors: Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.|MD Anderson International Foundation, Madrid, Spain.
authors: Pablo
authors: P
authors: García-Sanz
authors: Biomedical Research Group in Gynaecology, Vall d'Hebron Research Institute and Hospital, and Universitat Autonoma de Barcelona, Barcelona, Spain.
authors: Irene
authors: I
authors: Campoy
authors: MD Anderson Cancer Center Madrid, Madrid, Spain.
authors: Alejandro
authors: A
authors: Rojo-Sebastián
authors: Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
authors: Sonia
authors: S
authors: Gatius
authors: Department of Pathology, Hospital Universitario Vall Hebron, Barcelona, Spain.
authors: Ángel
authors: Á
authors: García
authors: MD Anderson Cancer Center Madrid, Madrid, Spain.
authors: Luis
authors: L
authors: Chiva
authors: MD Anderson Cancer Center Madrid, Madrid, Spain.
authors: Sonsoles
authors: S
authors: Alonso
authors: Biomedical Research Group in Gynaecology, Vall d'Hebron Research Institute and Hospital, and Universitat Autonoma de Barcelona, Barcelona, Spain.|Department of Obstetrics and Gynaecology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors: Antonio
authors: A
authors: Gil-Moreno
authors: Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
authors: Xavier
authors: X
authors: González-Tallada
authors: Biomedical Research Group in Gynaecology, Vall d'Hebron Research Institute and Hospital, and Universitat Autonoma de Barcelona, Barcelona, Spain.|Department of Obstetrics and Gynaecology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors: Berta
authors: B
authors: Díaz-Feijoo
authors: Hospital Universati de Bellvitge, Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), Barcelona, Spain.
authors: August
authors: A
authors: Vidal
authors: First Chair and Department of Gynaecological Oncology and Gynaecology, Medical University of Lublin, Lublin, Poland.
authors: Patrycja
authors: P
authors: Ziober-Malinowska
authors: First Chair and Department of Gynaecological Oncology and Gynaecology, Medical University of Lublin, Lublin, Poland.
authors: Marcin
authors: M
authors: Bobiński
authors: Translational Medical Oncology, Health Research Institute of Santiago (IDIS), SERGAS, Santiago, Spain.
authors: Rafael
authors: R
authors: López-López
authors: Translational Medical Oncology, Health Research Institute of Santiago (IDIS), SERGAS, Santiago, Spain.
authors: Miguel
authors: M
authors: Abal
authors: Hospital Universati de Bellvitge, Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), Barcelona, Spain.|Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, Barcelona, Spain.
authors: Jaume
authors: J
authors: Reventós
authors: Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.|Hospital Universati de Bellvitge, Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), Barcelona, Spain.
authors: Xavier
authors: X
authors: Matias-Guiu
authors: Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.|MD Anderson International Foundation, Madrid, Spain.
authors: Gema
authors: G
authors: Moreno-Bueno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002296:Carcinosarcoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D014599:Uterus / Q000473:pathology*