Molecular alterations in endometrial cancer: implications for clinical management

Over the last decades, advances have been made in the treatment of endometrial cancer. The clinicopathological risk stratification for postoperative therapy has considerably reduced overtreatment by refining indications and introducing treatment with fewer side effects. Despite refinement in the use of postoperative radiation therapy in EC, over- and under- treatment remain a clinical problem. This may be caused by the limited accuracy of the clinicopathological risk stratification to select patients of higher risk of recurrence. The lack of reproducibility of pathologists to diagnose tumor type and grade may also limit the accuracy of the clinicopathological risk stratification. Expert gyneco-pathology review and a two-tiered grading system will lead to more accurate and reproducible diagnoses. Nonetheless, there is pressing need to understand tumor behavior and design tailored treatments to further improve risk stratification. The identification of molecular markers predictive of recurrence risk or treatment benefit beyond current clinicopathological factors would represent a major advance. The aims of this thesis were to gain insight in the molecular alterations of endometrial cancer and to identify prognostic markers in endometrial cancer to refine clinicopathological risk assessment and direct adjuvant therapy.