Endometrial Cancer, Endometrial Neoplasm
Conditions
Keywords
endometrial cancer, molecular classification, POLEmut subgroup
Brief summary
In recent years, knowledge about cancer biology has expanded significantly. The study of gene expression profiles has revealed the heterogeneous nature and potential reclassification of the various tumor subtypes based on specific genetic alterations. This is of great importance since it allows a therapeutic approach more directed to the intrinsic characteristics of each tumor (precision medicine). Integrating clinicopathological information with molecular classification could provide new guidelines when approaching patients with EC, both in preoperative assessment and in adjuvant treatment and surveillance. The application of molecular classification in endometrial carcinomas shows a subgroup of patients with an excellent prognosis, corresponding to the POLEmut subgroup that could be reclassified with eventual therapeutic de-escalation. The clinical guidelines for the management of patients with endometrial cancer proposed by ESGO/ESTRO/ESP in 2020 recommend the use of this new classification, and warn that clinical management may be modified by the molecular classification in scenarios where adjuvant chemotherapy is considered (high-grade/high-risk disease).
Interventions
None listed
Sponsors
CEMIC Buenos Aires
Hospital Italiano de Buenos Aires
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 18 years of age with a diagnosis of EC diagnosed by histological biopsy and surgically treated sequentially in the participating centers in the last 5 years with clinical follow-up. * Patients over 18 years of age, diagnosed with CE III-IV by histological biopsy, not susceptible to surgical treatment in each institution during the last 5 years in clinical follow-up. Cases with a diagnosis of carcinosarcoma (a rare subtype of endometrial carcinoma with sarcomatous transdifferentiation) are included. * Material blocks fixed in formalin and embedded in paraffin with a tumor volume in the paraffin block of at least 1 cm3
Exclusion criteria
* The following uterine neoplasms will be excluded: * Biphasic tumors (epithelial-mesenchymal) such as adenosarcoma. * Mesenchymal neoplasms such as endometrial stromal sarcoma and leiomyosarcomas. * Others: primary lymphoproliferative processes of the uterine body; neuroendocrine tumors; Gestational trophoblastic disease, secondary lesions either of the genital tract (example: cervical carcinomas with extension to the endometrium) or of distant sites (breast cancer metastasis). * Patients with synchronous endometrial and ovarian carcinoma * For technical reasons, they will be excluded * tumors smaller than 0.2 cm in which sufficient material cannot be obtained for immunohistochemical and molecular biology determinations. * Tumors with severe artifacts due to poor processing, such as autolysis. * Samples with low-quality DNA * Patients operated on outside participating centers. * Patients under 18 years of age. * Patients with primary non-surgical treatments (neoadjuvant chemotherapy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of Endometrial Cancer Molecular Subtypes Identified by Immunohistochemistry and POLE Sequencing | At study inclusion (retrospective evaluation of cases from the last 5 years). Units: Percentage of patients per subtype | Proportion of patients in each of the four molecular subtypes of endometrial cancer (POLE-ultramutated, microsatellite instability hypermutated, copy-number low, copy-number high) determined using immunohistochemistry for MMR proteins and TP53, and NGS-based sequencing of the POLE gene. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association Between Molecular Subtypes and Histological Risk Categories. | At study inclusion (retrospective evaluation of cases from the last 5 years). | Proportion of patients with low- versus high-risk histological types within each molecular subtype. |
| Time to Recurrence by Molecular Subtype | At study inclusion (retrospective evaluation of cases from the last 5 years). | Time (in months) from diagnosis to first documented relapse, stratified by molecular subtype. |
Contacts
Primary ContactHernan García Rivello MD, PhD
Backup ContactRomina Albite D Bsc, Phd
Outcome results
None listed