Mutational analysis of the PTEN gene in endometrial carcinoma and hyperplasia

To determine the potential role of PTEN in the process of endometrial carci nogenesis, we examined a series of endometrial carcinoma and hyperplasia of the uterine corpus for the presence of a PTEN mutation. The entire coding region of the gene was screened for the presence of mutations by single-str and conformation polymorphism analysis, and mutations were confirmed by seq uencing. We detected mutations in 14 of 57 endometrial carcinomas (13 of 50 endometrioid adenocarcinomas and 1 of 7 nonendometrioid adenocarcinomas) a nd 7 of 73 endometrial hyperplasias (1 of 24 simple hyperplasias without at ypia, none of 16 complex hyperplasias without atypia, and 6 of 33 complex h yperplasias with atypia). Most (88%) mutations were clustered in exons 5, 7 and 8. Of the 24 mutations detected in 21 cases, 12 were frameshifts, 9 we re nonsense, 2 were missense, and I was a silent mutation, patients with a PTEN mutation had a better prognosis than those with no PTEN mutation. The presence of PTEN mutations in hyperplasia suggests that PTEN inactivation m ay occur as an initiating event in endometrial carcinogenesis and is involv ed in the development of cytologic atypia in hyperplasia.