We conclude from the present study, to our knowledge the most comprehensive molecular characterization of specimens ranging from precursors through primary to metastatic EEC lesions, that PTEN mutations and loss, mutations in PIK3CA as well as PI3K and KRAS signaling activation are early events in the development from CAH to EEC, while hormone receptor loss and EMT occur during dedifferentiation. This evidence concerns the gene PTEN and exstrophy-epispadias complex.