Molecular pathology of endometrial carcinoma and its histopathological correlations. Beyond a dualistic vision

Endometrial cancer (EC) accounts for about 4% of all female cancers and affects mainly postmenopausal women, representing a constantly growing disease especially in Western countries. Traditionally considered an indolent disease treated by surgery, it shows heterogeneous histological types, often presenting in advanced stages with greater biological aggressiveness. The dualistic classification proposed by Bokhman more than thirty years ago and confirmed by pivotal studies by Kurman et al. appears inadequate today, especially in light of numerous molecular studies. New perspectives on the pathogenesis and progression of EC appear to be have been supplied by recent genomic studies. Recently, TCGA (Cancer Genome Atlas Research Network) has divided ECs into 4 genomic classes: ultra-mutated POLE, microsatellite instability, low copy number, and serous “like” with a high number of copies. This classification seems to open up new opportunities in individualized therapeutic strategies. In this chapter, an extensive review of the main molecular markers involved in the pathogenesis and progression of EC is presented, including steroid hormone receptors, PTEN, PIK3CA, beta-catenin, E-cadherin, BCL-2, Cyclin D1, K- RAS, p53, p16, HER2/neu, Ki67, IMP3, ARID1A, C-myc, angiogenic factors, FGFR2, HGF, C-MET and MSI. Particular attention is given to the correlation between the different histological types and their possible implications for prognosis and individualized therapy