Molecular pathology of endometrial cancer: recent advances in classification, prognostication, and management

Abstract

Endometrial carcinoma is the most common gynaecological malignancy in the UK and its incidence is increasing worldwide. The classification of endometrial carcinoma (EC) has been based on cell type (histotype) for decades, and this, together with grade, lymphovascular space invasion (LVSI) and stage of the tumor was used for risk assessment, guiding decisions about the extent of surgery and the need for post-surgical adjuvant treatment. There has been, and remains, considerable variation in clinical practice worldwide, with respect to both the extent of surgery (lymph node dissection, omentectomy, pelvic washings) and use of adjuvant therapy (radiation, chemotherapy, or both) for patients with identical risk factors but treated at different centers. Furthermore, EC has tended to be treated as a single disease, irrespective of histotype. In the past five years there has been a significant move to more personalized risk assessment and treatment with the introduction of routine molecular assessment of EC, and diagnosis of molecular subtype. The four EC molecular subtypes differ with respect to molecular pathology, genetic and environmental risk factors, precursor lesions, prognosis and response to specific treatments. This review will discuss the assessment of EC molecular subtype in clinical practice and how this information impacts on risk assessment and treatment.