Genetic analysis of uterine aspirates improves the diagnostic value and captures the intra-tumor heterogeneity of endometrial cancers
Mota A (1,2), Colás E (3), García-Sanz P (1,2), Campoy I (4), Rojo-Sebastián A (5), Gatius S (3), García Á (6), Chiva L (5), Alonso S (5), Gil-Moreno A (4,7), González-Tallada X (3), Díaz-Feijoo B (4,7), Vidal A (8), Ziober-Malinowska P (9), Bobiński M (9), López-López R (10), Abal M (10), Reventós J (8,11), Matias-Guiu X (3,8), Moreno-Bueno G (1,2). 1Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPAZ, Madrid, Spain.
2MD Anderson International Foundation, Madrid, Spain.
3Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
4Biomedical Research Group in Gynaecology, Vall d'Hebron Research Institute and Hospital, and Universitat Autonoma de Barcelona, Barcelona, Spain.
5MD Anderson Cancer Center Madrid, Madrid, Spain.
6Department of Pathology, Hospital Universitario Vall Hebron, Barcelona, Spain.
7Department of Obstetrics and Gynaecology, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
8Hospital Universati de Bellvitge, Institut d'Investigacions Biomèdiques de Bellvitge (IDIBELL), Barcelona, Spain.
9First Chair and Department of Gynaecological Oncology and Gynaecology, Medical University of Lublin, Lublin, Poland.
10Translational Medical Oncology, Health Research Institute of Santiago (IDIS), SERGAS, Santiago, Spain.
11Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, Barcelona, Spain.
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.
CITATION Mod Pathol. 2016 Sep 2. doi: 10.1038/modpathol.2016.143