Molecular pathogenesis of endometrial cancer

Introduction. Genetic changes which cause endometrial cancer may be discovered by simple comparison of tumor with normal tissues, and correlating clinicopathologic with genotypic features. More difficult is the specific elaboration of those interacting events which may transpire in a particular sequence during a protracted interval of carcinogenesis. A small burden of premalignant cells makes them elusive targets for study, and their histopathologic plasticity complicates achieving diagnostic consensus and reproducibility between laboratories. Despite these formidable obstacles, the last decade has seen an explosion of new data regarding endometrial carcinogenesis. Cancer subtypes have been clearly divided along genetic and clinical lines, and a flood of information about those genetic changes which cause endometrial cancer has been forthcoming from many sources, including non-gynecologic tumor systems. The diagnosis of premalignant endometrial lesions, long a confusing and contentious issue among pathologists, has achieved objectivity from biomarker studies and histomorphometric analysis. These data have yielded a scientific basis for standardization and revision of endometrial precancer diagnosis in a routine diagnostic setting. Lastly, experimental access to preclinical stages of premalignant endometrial disease, a phase of tumorigenesis which is the probable mediator of endocrine risk factors, affords an opportunity for cancer chemoprevention.