We immunohistochemically analyzed 89 endometrial carcinomas for insulin-like growth factor-I receptor (IGF-IR) and PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression. Results were compared with clinicopathologic factors, bcl-2 and bax expression, microsatellite instability (MSI) status, and prognosis. Increased expression of IGF-IR and bcl-2 (> 50% cells) was seen in 60 cases (67%) and 15 cases (17%), respectively; loss of PTEN was seen in 13 cases (15%) and of bax in 11 cases (12%). No significant correlation was observed between the proteins or with clinicopathologic factors. Loss of PTEN was more frequent in MSI-positive tumors (4/10 [40%]) than in negative tumors (9/79 [11%]; P = .016). Longer survival was observed for patients with endometrioid tumors, International Federation of Gynecology and Obstetrics stage I or II tumors, grade 1 tumors, superficial myometrial infiltration (< or = 50%), less than 5% necrosis, no vascular invasion, or low level IGF-IR (< 10% of cells) (P < or = .05). Cox analysis showed independent value only for stage, grade, type, and lymph-vascular invasion (P < .05). Our data demonstrate that IGF-IR overexpression occurs in a subset of endometrioid carcinomas, which has potential prognostic value, while loss of PTEN often is associated with the MSI phenotype.