• Daniela Kandioler, Sebastian F Schoppmann, Ronald Zwrtek, Sonja Kappel, Brigitte Wolf, Martina Mittlböck, Irene Kührer, Michael Hejna, Ursula Pluschnig, Ahmed Ba-Ssalamah, Fritz Wrba, and Johannes Zacherl.
• Department of Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: daniela.kandioler@meduniwien.ac.at.
• J. Thorac. Cardiovasc. Surg. 2014 Nov 1; 148 (5): 2280-6.

BackgroundFluorouracil 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.ObjectiveTo test the value of TP53 as a biomarker prognosing outcome in patients with neoadjuvantly treated esophageal cancer.Patients And MethodsThe 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).ResultsMutations 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).ConclusionsThe 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.Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

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