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

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

Author information

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.

PMID:
25135238
DOI:
10.1016/j.jtcvs.2014.06.079
[Indexed for MEDLINE]
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