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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 2/2010

01-02-2010 | Translational Research and Biomarkers

p53 Genotype Predicts Response to Chemotherapy in Patients with Squamous Cell Carcinoma of the Esophagus

Authors: Makoto Yamasaki, MD, PhD, Hiroshi Miyata, Yoshiyuki Fujiwara, Shuji Takiguchi, Kiyokazu Nakajima, Toshirou Nishida, Takushi Yasuda, Jin Matsuyama, Masaki Mori, Yuichiro Doki

Published in: Annals of Surgical Oncology | Issue 2/2010

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Abstract

Background

Response to chemotherapy and anatomical spread are significant prognostic factors in patients with esophageal squamous cell carcinoma (ESCC) treated by chemotherapy then surgery. Predicting the response to chemotherapy would allow significant optimization of cancer treatment.

Methods

Genomic mutation and protein expression of p53 were investigated retrospectively by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and immunohistochemistry (IHC) using biopsy specimens from 77 ESCC patients before chemotherapy with 5-fluorouracil, adriamycin, and cisplatin. p53 status was correlated with various clinicopathological factors. Thereafter, we performed a prospective study of 20 consecutive patients to test our prediction model.

Results

The retrospective study showed mutant p53 genotype and positive p53 IHC staining in 46.8 and 55.8% of patients, respectively, which was not associated with patient’s clinicopathological findings including initial tumor stage. Objective response to chemotherapy was observed in 65.9% of patients with wild genotype, but in only 16.7% of patients with mutant genotype. Patients with mutations in p53 therefore showed significantly poorer prognosis than those without mutant p53. In contrast, p53 IHC staining did not correlate with response to chemotherapy, curative resection rate or prognosis. In the prospective study, p53 mutation was seen in 50% (10/20) of patients and was again consistently associated with poorer response to chemotherapy and poorer prognosis.

Conclusions

p53 genotype of pretreatment biopsy is a potentially useful predictor of response to chemotherapy and prognosis in ESCC patients. This information might be valuable to clinicians in deciding on the optimal clinical strategy in patients with ESCC.
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Metadata
Title
p53 Genotype Predicts Response to Chemotherapy in Patients with Squamous Cell Carcinoma of the Esophagus
Authors
Makoto Yamasaki, MD, PhD
Hiroshi Miyata
Yoshiyuki Fujiwara
Shuji Takiguchi
Kiyokazu Nakajima
Toshirou Nishida
Takushi Yasuda
Jin Matsuyama
Masaki Mori
Yuichiro Doki
Publication date
01-02-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 2/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0851-4

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