Endometrial Cancer: Transitioning from Histology to Genomics

Abstract

Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013 and subsequent studies using immunohistochemistry have led to the current EC molecular classification into: polymerase epsilon mutated (POLEmut), p53 abnormal (p53abn), mismatch repair deficient (MMRd), and no specific molecular profile (NSMP). The four groups have prognostic value and represent a promising tool for clinical decision-making regarding adjuvant treatment. Molecular classification was integrated into the recent European Society of Gynecologic Oncology (ESGO) management guidelines. POLEmut EC has favorable outcomes and retrospective studies found that omitting adjuvant treatment is safe in this group; two prospective clinical trials, PORTEC-4 and TAPER, are ongoing to assess this. p53 abn is associated with increased recurrence, decreased survival, and benefitted from chemotherapy in the PORTEC-3 subgroup molecular analysis. The clinical trials PORTEC-4a and CANSTAMP will prospectively assess this. MMRd and NSMP groups have intermediate prognosis and will likely continue to rely closely on clinicopathological features for adjuvant treatment decisions. In addition, the molecular classification has led to exploring novel treatments such as checkpoint inhibitors. Overall, the molecular perspective on EC and associated clinical trials will likely refine EC risk stratification to optimize care and avoid overtreatment.

Endometrial carcinosarcoma

“…However, we have to point out that no prospective randomized studies ave validated the predictive value of adoption of the genomic/molecular profiling (with the except of MIS-H, being an agnostic marker supporting the adoption of immunotherapy) 18. Validation studies are still ongoing 14 15 19…”

Incorporación de avances en el diagnóstico y la caracterización del cáncer de endometrio: un beneficio para nuestras pacientes del cual aún estamos al debe

“…y donde la ausencia de expresión de receptores de estrógenos conllevaría peor pronóstico 12 . Es por ello por lo que el manejo actual del cáncer de endometrio va más allá de definir con hematoxilina y eosina el tipo histológico o el grado de diferenciación, sino que se mueve fuertemente a incorporar la caracterización molecular cuando se puedan identificar subtipos de cáncer de endometrio, que pese a tener un denominador común histológico, tipo endometrioide (en particular de alto grado), pueden tener un riesgo por completo distinto y con necesidad de adyuvancia diametralmente distinta 14,15 . Es imperativo que estos avances se incorporen a las guías nacionales de manejo con el fin de impactar positivamente en los recursos asignados, la oportunidad y la calidad del tratamiento ofrecido a nuestras pacientes.…”

Importance of the endometrial immune environment in endometrial cancer and associated therapies

“…Since their conception, validation and confirmation of the ProMisE molecular subtypes has been conducted to identify whether these subtypes have different therapeutic outcomes. This topic has been recently comprehensively reviewed by Mitric and Bernardini ( 13 ). For example, the PORTEC3 clinical trial investigated the benefit of adjuvant combined chemotherapy and radiotherapy compared to chemotherapy alone in patients with high grade and/or stage endometrial cancer ( 14 ).…”