The Expressions of MDM2 and P53 Protein are Adverse Prognostic Factors in Patients with Esophageal Squamous Cell Carcinoma

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is the fourth most prevalent malignancy in China and causes a high rate cancer-related death. In the present study, we aimed to examine the expression levels of MDM2 and P53 in different cell populations of tumor environments and explore their association with survivals of ESCC patients. Method: The protein expression and amplification of MDM2 and P53 were measured by immunochemistry and fluorescence in situ hybridization (FISH) in tumor specimens from 157 resected ESCC. Correlation analyses and independent prognostic outcomes were determined using Pearson's chi-square test and Cox regression analysis. Findings: We found that high expression levels of MDM2 in tumor cells were correlated with M status (P = 0.027), and high expression levels of P53 in tumor cells were positively closely correlated with N status (P = 0.005), M status (P = 0.008) and clinical stage (P = 0.003). The Kaplan-Meier survival analysis showed the ESCC patients with lower expression levels of MDM2 or P53 in tumor cells had better DFS and OS. Besides, the patients with the double high expression levels of MDM2 and P53 in tumor cells had worst DFS and OS compared to the patients with single high expression level of MDM2 or P53 in tumor cells or double low expression level of MDM2 and P53 in tumor cells (P<0.001 and P <0.001, respectively). Furthermore, the multivariate Cox model analysis determined the expression of MDM2, P53 and combined expression of MDM2 and P53 in tumor cells were independent predictors for DFS and OS in ESCC patients. Interpretation: The present study indicates that high expression of MDM2 and P53 are independently significant prognostic indicator of a higher rate of clinical stage and poor survival in patients with surgically resected ESCC. Funding Statement: The authors state: No specific funding was disclosed. Declaration of Interests: The authors have declared that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Research Ethics Committee of the Sun Yat-Sen University Cancer Center. Informed consent was obtained from all patients prior to specimen collection.