Daniela Kandioler1, Sebastian F Schoppmann2, Ronald Zwrtek3, Sonja Kappel4, Brigitte Wolf4, Martina Mittlböck5, Irene Kührer6, Michael Hejna6, Ursula Pluschnig6, Ahmed Ba-Ssalamah7, Fritz Wrba8, Johannes Zacherl9. 1. Department of Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: daniela.kandioler@meduniwien.ac.at. 2. Department of Surgery, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center-GI Tumor Unit, Medical University of Vienna, Vienna, Austria. 3. Department of Surgery, Landesklinikum Sankt Poelten, Sankt Poelten, Austria. 4. Department of Surgery, Medical University of Vienna, Vienna, Austria; Surgical Research, Medical University of Vienna, Vienna, Austria. 5. Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, Vienna, Austria. 6. Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria. 7. Department of Radiology, Medical University of Vienna, Vienna, Austria. 8. Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria. 9. Department of Surgery, Medical University of Vienna, Vienna, Austria.
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. 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.
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 cancerpatients 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: Kelly R Haisley; James P Dolan; Susan B Olson; Sergio A Toledo-Valdovinos; Kyle D Hart; Gene Bakis; Brintha K Enestvedt; John G Hunter Journal: J Gastrointest Surg Date: 2016-08-25 Impact factor: 3.452
Authors: Fiebo J C Ten Kate; Lucia Suzuki; Lambert C J Dorssers; Winand N M Dinjens; David T W Jones; Daan Nieboer; Michael Doukas; J Jan B Van Lanschot; Bas P L Wijnhoven; Leendert H J Looijenga; Katharina Biermann Journal: Oncotarget Date: 2017-10-24