Reclassifying endometrial carcinomas with a combined morphological and molecular approach

Currently, endometrial carcinoma diagnosis is based on morphology, often supplemented by immunohistochemistry. However, especially with high-grade endometrial carcinomas, there is considerable interobserver variability in diagnosis calling into question the value of morphology in stratifying these tumours into different prognostic and therapeutic groups. The purpose of this review is to provide an update on the recently described molecular classification of endometrial carcinoma.

In 2013, the Cancer Genome Atlas (TCGA) published a seminal molecular study of endometrial carcinomas of endometrioid, serous and mixed types. This revealed that endometrial carcinoma consists of four intrinsic molecular subtypes: POLE (ultramutated), microsatellite instabilty (hypermutated), copy-number low (also referred to as microsatellite stable or no specific molecular profile) and copy-number high (serous-like). These four molecular subtypes are of prognostic significance with POLE tumours having the best and copy-number high, the worst prognosis.

It is likely that TCGA classification will become the mainstay of endometrial carcinoma diagnosis in the coming years and various strategies (Proactive Molecular Risk Classifier for Endometrial Cancer and the TransPORTEC classifiers) have been proposed for a combined morphological-molecular classification which can be undertaken in most pathology laboratories. This will necessitate routine undertaking of POLE mutation analysis in some endometrial carcinomas and require an appropriate infrastructure.