Molecular identification of latent precancers in histologically normal endometrium

Discovery of somatically mutated cells in human tissues has been less frequ ent than would be predicted by ill vitro mutational rates. We analyzed the PTEN tumor suppressor gene as an early marker for endometrial carcinogenesi s, and we show that 43% of histologically normal premenopausal endometria c ontain rare glands that fail to express PTEN protein because of mutation an d/or deletion. These persist between menstrual cycles. Histopathology of PT EN-null glands is initially unremarkable, but with progression, they form d istinctive high-density clusters. These data are consistent with a progress ion model in which initial mutation is not rate limiting.