Endometrial cancer (EC) is the most common gynecologic cancer and the current methods for the prediction of its prognosis and treatment response are unfortunately suboptimal. In this study, we evaluated the prognostic value of p53, Pirh2, and L1CAM in 60 cases of EC using im munohistochemistry (IHC) and polymerase chain reaction. TP53 missense mutations result in nuclear accumulation of p53 protein that can be detected as overexpression by IHC. This is in the form of diffuse strong nuclear positivity involving at leastatleast>50% of the tumor cells as a whole or if >50% of the tumor cells of a discrete geographical areas. Abnormal p53 IHC expression was expressed in 33.3% of the cases and significantly associated with the tumor grade, myometrial in vasion (MI), lymphovascular invasion (LVSI), nodal meta stasis, and FIGO stage, and the advanced European Society for Medical Oncology (ESMO) risk groups (P<0.001 for each). High IHC Pirh2 expression was noted in 58.3% of the cases, and significantly associated with MI, LVSI, nodal metastasis, FIGO stage, and high-risk group (P<0.001, P=0.011, P=0.010, P=0.024, P=0.005, respectively). There was a significant upregulation of Pirh2 mRNA expression in ECspecimens as comparedwith the control adjacent tissues (P=0.001). Upregulated Pirh2 mRNA expression had a sig nificant association with Pirh2 immunostaining, tumor grade, tumor stage, MI, lymph node involvement, LVSI, and relapse (P<0.001 for each). Positive L1CAM immunoexpression was noted in 26.7% and was significantly associated with grade, MI, LVSI, nodal metastasis, FIGO stage, and high-risk group (P=0.003, P=0.023, P=0.003, P<0.001, P<0.001, P=0.002, respectively). Analysis of follow-up period revealed that EC with abnormal p53 IHC expression, high pirh2 and positive L1CAM expression exhibited a potent relation with tumor relapse, shorter overall survival and disease-specific