Molecular stratification or clinical necessity? The role of dMMR status in endometrial cancer

Endometrial cancer (EC) is one of the most common malignant tumors of the female reproductive system. Traditional clinicopathological factors do not always adequately reflect tumor biology, making molecular stratification increasingly important. A key element of this approach is the assessment of mismatch repair deficiency (dMMR) and microsatellite instability (MSI).

Aim of this work is to summarize current evidence on the clinical value of dMMR testing in EC and to define when and in whom it should be performed.

dMMR / MSI tumors account for approximately 20–30 % of EC cases. Testing provides several critical benefits: 1) identification of a distinct molecular subtype with characteristic biological behavior and intermediate prognosis; 2) early diagnosis of Lynch syndrome, enabling timely preventive strategies for patients and their relatives; 3) guidance in therapeutic decision-making, since dMMR / MSI tumors are highly sensitive to PD-1 inhibitors. Current international guidelines recommend that all patients with newly diagnosed EC undergo dMMR testing, regardless of age, family history, or histological subtype. This universal approach improves risk stratification, allows identification of hereditary cancer syndromes, and ensures access to effective immunotherapy in recurrent or metastatic settings