Endometrial cancer (EC) has historically been classified through histology into endometrioid (type 1) and non-endometrioid (type II, mainly serous) subtypes, although it 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 genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes: polymerase (POLE) ultramutated, microsatellite unstable, copy number low/microsatellite stable, and copy number high/¿serous-like¿. Through the analysis of surrogate markers (POLE, MSI, and p53), it has been validated a more cost-effective and clinically applicable methods for this molecular classification using targeted sequencing and immu- nohistochemistry on formalin-fixed paraffin-embedded tumor samples. In this way the molecular classification could be integrated in the gynaecological pathology practice. The possibility to obtain an integrated molecular risk profile using these subtypes, could have prognostic implications and may identify patients who could benefit from additional treatment because of a higher risk of recurrence. The aim of this study is to assess the prognostic value of this molecular classification to determine if molecular subtypes, with or without additional clinical and pathological parameters, may influence the management of women with endometrial cancer.
The majority of endometrial cancers are diagnosed early (80% in stage I), with 5-year survival rates of over 95%. However, 5-year survival rates are much lower if there is regional spread or distant disease (68% and 17%, respectively). Predicting these patients¿ life expectancy is thus important for clinicians and patients. We know that tumor staging system, lymph node status, histological grade, depth of myometrial invasion and lymphovascular space invasion play an important role in the prediction of the PFS. From the new molecular classification, few studies have been published in literature about prognostic and predictive implications of different molecular subtypes of EC. Our study aims to clarify whether the molecular classification of the EC impacts on PFS and OS and to help clinicians to assess whether patients can be managed differently based on the molecular classification. If this molecular classification will become an essential part of gynaecological pathology practice, it could influence treatment in the preoperative setting (lymphadenectomy yes or no), post-operative setting (adjuvant treatment yes or no), and could be exploited for surveillance advice or targeted treatment options in the recurrent or metastatic setting.