Clinically relevant histopathological features and biomarkers in endometrial cancer

To provide an overview of the most important histopathological characteristics and biomarkers of endometrial carcinoma that have clinical relevance for prognosis, prediction of treatment response, and decision-making regarding adjuvant therapy.

Endometrial carcinoma represents the most common malignancy of the female reproductive tract in developed countries. Disease prognosis is determined not only by the anatomical extent, but also by a number of non-anatomical factors. The histological tumour type, presence of lymphovascular space invasion, and specific patterns of myometrial invasion (such as the MELF pattern) play major roles. Current molecular classification divides endometrial carcinomas into four groups (POLEmut, MMRd, NSMP, and TP53mut), which differ in prognosis as well as in therapeutic response. Additional clinically applicable biomarkers include oestrogen and progesterone receptors, L1CAM, HER2, CA125, and HE4. Emerging research focuses on novel biomarkers such as TROP2, circulating tumour DNA (ctDNA), circular RNA (circRNA), tumour- -infiltrating lymphocytes (TILs), and folate receptor alpha (FRa). These markers enable more precise risk stratification and identification of patients suitable for targeted therapies. Integration of multiple biomarkers with clinicopathological parameters further enhances the accuracy of risk assessment and prediction of treatment response.

Incorporating histopathological features and biomarkers into routine clinical practice allows for a more accurate estimation of prognosis and a more rational selection of adjuvant therapy. An increasing number of non-anatomical biomarkers are becoming an integral part of the decision-making algorithm in endometrial carcinoma management.