title: The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: daniela.kandioler@meduniwien.ac.at.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kandioler
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center-GI Tumor Unit, Medical University of Vienna, Vienna, Austria.
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.affiliation: Department of Surgery, Landesklinikum Sankt Poelten, Sankt Poelten, Austria.
authors.forename: Ronald
authors.initials: R
authors.lastname: Zwrtek
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria; Surgical Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kappel
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria; Surgical Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wolf
authors.affiliation: Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Mittlböck
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Kührer
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hejna
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Pluschnig
authors.affiliation: Department of Radiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ba-Ssalamah
authors.affiliation: Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zacherl
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001317:Austria; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D005472:Fluorouracil