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

Histopathology. 2020 Dec;77(6):963-973. doi: 10.1111/his.14208. Epub 2020 Sep 30.

Abstract

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.

Keywords: fluorescence in-situ hybridisation; improved prognosis; mouse double minute 2 amplification; oesophageal squamous cell carcinoma; stages I-II disease.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Squamous Cell Carcinoma of Head and Neck* / diagnosis
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-mdm2