The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study

J Thorac Cardiovasc Surg. 2014 Nov;148(5):2280-6. doi: 10.1016/j.jtcvs.2014.06.079. Epub 2014 Jul 22.


Background: Fluorouracil and cisplatin have been used most frequently as neoadjuvant therapy for esophageal cancer. Both drugs are believed to act via a p53-dependent apoptosis pathway. The TP53 gene is frequently mutated in esophageal cancer.

Objective: To test the value of TP53 as a biomarker prognosing outcome in patients with neoadjuvantly treated esophageal cancer.

Patients and methods: The investigation included 36 patients with primary operable esophageal cancer who were treated neoadjuvantly with cisplatin and fluorouracil. The TP53 genotype was assessed from paraffin-embedded diagnostic tumor biopsies using a standardized gene-specific TP53 sequencing protocol (mark53 kit; mark53 Ltd, Vienna, Austria).

Results: Mutations in the TP53 gene were present in 50% of tumors. Two-year overall survival rates were 55.6% in patients with a normal TP53 marker status, compared with 16.7% in those with a mutant TP53 gene. In patients with normal TP53, neoadjuvant treatment resulted in significant advantages in terms of tumor-associated survival (P=.0049) and overall survival (P=.0304) compared with those with mutant TP53. The median tumor-associated survival was 34.2 months for patients with normal TP53, compared with 8.9 months for those with mutant TP53. The latter had a 3-fold higher risk of dying (hazard ratio, 3.01; 95% confidence interval, 1.359-6.86).

Conclusions: The biomarker TP53 divides esophageal cancer patients into 2 categories with markedly different outcomes: patients with a normal TP53 marker status may experience notable benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil, whereas those with a mutant TP53 marker status appear to be at risk for lack of response.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Austria
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • DNA Mutational Analysis
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophagectomy
  • Female
  • Fluorouracil / administration & dosage
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation*
  • Neoadjuvant Therapy*
  • Phenotype
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*


  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cisplatin
  • Fluorouracil

Supplementary concepts

  • Adenocarcinoma Of Esophagus