p53 overexpression is a prognosticator of poor outcome in esophageal cancer

Melling,Nathaniel; Norrenbrock,Sonja; Kluth,Martina; Simon,Ronald; Hube‑Magg,Claudia; Steurer,Stefan; Hinsch,Andrea; Burandt,Eike; Jacobsen,Frank; Wilczak,Waldemar; Quaas,Alexander; Bockhorn,Maximillian; Grupp,Katharina; Tachezy,Michael; Izbicki,Jakob; Sauter,Guido; Gebauer,Florian

doi:10.3892/ol.2019.10020

p53 overexpression is a prognosticator of poor outcome in esophageal cancer

Authors:
- Nathaniel Melling
- Sonja Norrenbrock
- Martina Kluth
- Ronald Simon
- Claudia Hube‑Magg
- Stefan Steurer
- Andrea Hinsch
- Eike Burandt
- Frank Jacobsen
- Waldemar Wilczak
- Alexander Quaas
- Maximillian Bockhorn
- Katharina Grupp
- Michael Tachezy
- Jakob Izbicki
- Guido Sauter
- Florian Gebauer
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Affiliations: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg‑Eppendorf, D‑20246 Hamburg, Germany, Institute for Pathology, University Medical Center Hamburg‑Eppendorf, D‑20246 Hamburg, Germany, Institute for Pathology, University Hospital Cologne, D‑50937 Cologne, Germany, Department of Surgery, University Hospital Cologne, D‑50937 Cologne, Germany
Published online on: February 6, 2019 https://doi.org/10.3892/ol.2019.10020
Pages: 3826-3834
Copyright: © Melling et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Immunohistochemistry studies on p53 inactivation in esophageal cancer are available with inconclusive results. Data on the combined effect of p53 protein accumulation and TP53 genomic deactivation in large scale studies for esophageal cancer are currently lacking. A tissue microarray with 691 esophageal cancer samples was analyzed by p53 immunohistochemistry and fluorescence in situ hybridization (FISH). Nuclear p53 accumulation was observed in 45.9% of patients with adenocarcinoma (AC) and in 40.0% in squamous cell carcinoma (SCC). Heterozygous TP53 deletions occurred in 40.9% in AC and in 19.4% in SCC. Homozygous deletions did not occur at all. High‑level p53 immunostaining was associated with shortened overall survival in AC and SCC while TP53 deletions alone showed no correlation with survival. High‑level p53 immunostaining in patients with AC was associated with advanced tumor (P=0.019) and Union for International Cancer Control stages (P=0.004), grading (P=0.027) and the resection margin status (P=0.006). Associations between p53 immunostaining and SCC were not found. TP53 deletions were found to be associated with advanced tumor stages (P=0.028) and the presence of lymph node metastasis (P=0.009) in SCC. In conclusion, strong p53 immunostaining, but not TP53 deletion alone, is associated with unfavorable outcomes and may therefore represent a clinically useful molecular marker in esophageal cancer.

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