Mouse double minute 2 amplification in oesophageal squamous cell carcinoma is associated with better outcome

Abstract

Mouse double minute 2 amplification in oesophageal squamous cell carcinoma is associated with better outcome Aims: This study aimed to determine the frequency of mouse double minute 2 (MDM2) amplification in oesophageal squamous cell carcinomas (ESCC) and to clarify its prognostic significance. Methods and results: We investigated MDM2 amplification on tissue microarrays using fluorescence in-situ hybridisation and analysed its correlations with clinicopathological features and outcomes in 515 Chinese ESCC patients. MDM2 amplifications were found in 37 of 515 ESCC patients (7.2%). They were significantly negatively correlated with tumour size (P = 0.045), disease progression (P = 0.002) and death (P = 0.003). Univariate analysis showed that the following clinicopathological factors were associated with disease-free survival (DFS) and overall survival (OS): differentiation (P = 0.025 for DFS and P = 0.061 for OS), vessel invasion (P = 0.001 and P = 0.002), nerve invasion (P = 0.009 and P = 0.001), clinical stage (P < 0.001 and P < 0.001) and MDM2 amplification (P = 0.012 and P = 0.014). Multivariate Cox regression analysis showed that MDM2 amplification was an independent prognostic factor for improved outcomes (P = 0.023 for DFS, P = 0.027 for OS) and the clinical stage was an independent prognostic factor for poor outcomes (P < 0.001). When survival analyses were conducted at different clinical stages, MDM2 amplification was associated with longer DFS and OS in stages I-II ESCC (P = 0.003 for DFS and P = 0.003 for OS), but there was no significant survival difference in stages III-IVa ESCC. Conclusions: MDM2 amplification was significantly correlated with an improved patient outcome, especially in stage I and II disease, and was verified as an independent prognostic factor in our patients. Therefore, MDM2 amplification may be a potential biomarker for risk stratification of the lower stages of ESCC.

Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

“…[21][22][23][24] Multiple oncogenes are ampli ed in ESCC, including MDM2, ADAR1, EGFR, and c-MYC. [25][26][27][28] These ampli ed oncogenes are increasingly in uencing decision-making for precise cancer treatments. However, the clinical applications of the ampli cation of tumor suppressor genes in ESCC remain rare.…”

CDK4 Amplification in Esophageal Squamous Cell Carcinoma Associated With Better Patient Outcome

“…The perturbed cell cycle regulation pathway in ESCC mainly exhibited genetic alterations in the G1/S transition control, including mutations or deletions of TP53 , RB1 , CDKN2A , CHEK1 , and CHEK2 , and amplifications of CDK4 , CCND1 , CDK6 , and MDM2 ( Song et al, 2014 ). Alterations of these genes, such as inactivation of RB1 and CDKN2A and amplification of CCND1 , CDK6 , and MDM2 have been well documented in ESCC ( Huang et al, 2007 ; Baba et al, 2014 ; Jiang et al, 2020 ). To date, the prognostic significance of CDK4 amplification in ESCC has not been described before.…”