Prognostic Importance of PTEN, p53, and MDM2 Expressions in Endometrioid and Serous-Type Endometrial Carcinomas

Authors : Sibel Acat, Zeliha Esin Çelik, Abdül Hamid Güler, Cetin Celik

Pages : 528-536

Doi:10.37990/medr.1486449

View : 27 | Download : 75

Publication Date : 2024-09-24

Article Type : Research Paper

Abstract :Aim: Endometrial carcinomas (ECs) are neoplasms with the highest rate of change in the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. In this study, the relationship among PTEN, MDM2, and p53 protein expression in the PI3K/AKT/mTOR pathway with clinicopathological data in endometrioid endometrial carcinomas (EECs) and serous-type endometrial carcinomas (SECs) was evaluated. Material and Method: A hundred and twenty cases of patients who underwent hysterectomy for EC between 2009 and 2021 were included in the study. Thirty cases of SEC and 90 cases of EEC were evaluated. EEC cases consist of grades 1-3 tumors, and each group includes 30 patients. p53 was examined in two groups as normal/wild type and abnormal/mutant type. PTEN and MDM2 were examined in two groups: positive and negative. The relationship among p53, PTEN, and MDM2 immunohistochemical expression status with histological grade, myometrial invasion, cervical invasion, lymphovascular invasion (LVI), metastatic lymph nodes, presence of tumor in peritoneal fluid, tumor stage, and overall and progression-free survival was evaluated. Results: Loss of PTEN was associated with EEC compared to SEC (p<0.001). PTEN loss is mostly associated with p53 normal/wild type (p=0.038). MDM2 expression was associated with a lower histological grade (p<0.001) and stage (p=0.002). MDM2 expression was inversely associated with lymphovascular invasion (p=0.017), cervical invasion (p=0.040), and peritoneal fluid retention (p=0.018). In most cases showing MDM2 expression, p53 was found to be normal/wild type (p=0.011). p53 mutation was found to be associated with advanced age (p=0.002), SEC (p<0.001), high grade (p<0.001), high risk (p<0.001), advanced stage (p=0.002), adjuvant therapy (p=0.002), and peritoneal fluid involvement (p=0.002) and low overall (p=0.014) and progression-free survival (p=0.050). Conclusion: MDM2 expression was found to be associated with positive prognostic parameters. PTEN loss can be used to distinguish between EEC and SEC. p53 remains a critical determinant of prognosis in ECs.
Keywords : Endometrial carcinomas, PTEN, MDM2, p53, immunohistochemistry