Strickland AL, et al. - Several potential markers of endometrioid intraepithelial neoplasia (EIN) based rationally on molecular pathways most frequently misregulated in endometrial cancer—the 3-phosphoinositide kinase (PI3K)/AKT, β-catenin, and mismatch repair pathways— were investigated. In conjunction with 2 new markers—FOXO1 and phosphorylated AKT (pAKT)—PTEN, PAX2, β-catenin, and MLH1 were assessed in EIN. Immunohistochemistry was used to analyze the benign (n = 14) and EIN (n = 35) endometria. In normal endometria, FOXO1 was exhibited in the cytoplasm in proliferative phase, whereas in secretory phase, FOXO1 was nuclear, revealing the participation of PI3K/FOXO1 in endometrial cycling and that FOXO1 is a readout of PI3K status. Normal endometria exhibited low pAKT expression. The majority of EINs (27/35, 77%) exhibited altered FOXO1 or pAKT expression, with FOXO1 and pAKT being co-altered only in some (20/35, 57%). Further, clonal distinctiveness was observed in β-catenin or MLH1 in EINs, pointing the utility of these as markers in some cases. Researchers identified this study being the first to illustrate the potential of pAKT and FOXO1 as biomarkers in the histopathologic evaluation of EIN. However, interpretation was difficult due to variability in expression.