The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses

Abstract

Endometrial cancer is a clinically heterogeneous disease and it is becoming increasingly clear that this heterogeneity may be a function of the diversity of the underlying molecular alterations. Recent large-scale genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes, with well-described underlying genomic aberrations. These subtypes can be reliably delineated and carry significant prognostic as well as predictive information; embracing and incorporating them into clinical practice is thus attractive. The road towards the integration of molecular features into current classification systems is not without obstacles. Collaborative studies engaging research teams from across the world are working to define pragmatic assays, improve risk stratification systems by combining molecular features and traditional clinicopathological parameters, and determine how molecular classification can be optimally utilized to direct patient care. Pathologists and clinicians caring for women with endometrial cancer need to engage with and understand the possibilities and limitations of this new approach, because integration of molecular classification of endometrial cancers is anticipated to become an essential part of gynaecological pathology practice. This review will describe the challenges in current systems of endometrial carcinoma classification, the evolution of new molecular technologies that define prognostically distinct molecular subtypes, and potential applications of molecular classification as a step towards precision medicine and refining care for individuals with the most common gynaecological cancer in the developed world.

Incorporation of molecular characteristics into endometrial cancer management

“…We also discuss how the integrated molecular entities may provide clues to specific targeted treatment modalities that can be exploited in advanced‐stage or recurrent disease. For a more detailed background on the molecular EC classification, as well as assays that may be used for the diagnosis, the reader is referred to other reviews …”

“…For a more detailed background on the molecular EC classification, as well as assays that may be used for the diagnosis, the reader is referred to other reviews. [15][16][17] Endometrioid Endometrial Carcinoma (EEC),…”

The molecular pathology of cancer: from pan‐genomics to post‐genomics

“…For many cancers, these efforts have led to new, integrated classifications in which genomic and histological features often align in a striking and highly informative fashion. This is exemplified in the present Annual Review Issue (ARI) by updates on the classification of renal cell carcinoma (Hsieh et al ) and endometrial carcinoma (McAlpine et al ). Conversely, in addition to uncovering novel and highly relevant subtypes of many cancers, these studies have also revealed robust and biologically plausible commonalities between cancers arising in different organs, as shown by the comparison of clear cell carcinomas of the ovary and kidney by Ji et al .…”

Liquid Biopsy in Endometrial Cancer: New Opportunities for Personalized Oncology

“…The prognostic value of TCGA in EC has been corroborated in large cohorts included in studies developed by the Vancouver and PORTEC (Post Operative Radiation Therapy in Endometrial Carcinoma) groups [5,6]. This can be especially relevant in adjuvant treatment choices for high to intermediate-risk EC patients that are likely to be impacted by the integrated molecular classification [7], while recurrent disease may continue to represent an additional challenge. Despite these stratification conditionings, and as demonstrated in the majority of solid tumours, EC shows intratumour heterogeneity with different neoplastic cell components within the same tumour.…”