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

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

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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Authors and Affiliations

  1. Departments of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Makoto Yamasaki MD, PhD, Hiroshi Miyata, Yoshiyuki Fujiwara, Shuji Takiguchi, Kiyokazu Nakajima, Toshirou Nishida, Masaki Mori & Yuichiro Doki

  2. Department of Surgery, Kinki University School of Medicine, Osaka Sayama, Osaka, Japan

    Takushi Yasuda

  3. Department of Surgery, Yao Municipal Hospital, Yao, Osaka, Japan

    Jin Matsuyama

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  1. Makoto Yamasaki MD, PhD
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  2. Hiroshi Miyata
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  3. Yoshiyuki Fujiwara
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Correspondence to Makoto Yamasaki MD, PhD.

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Yamasaki, M., Miyata, H., Fujiwara, Y. et al. p53 Genotype Predicts Response to Chemotherapy in Patients with Squamous Cell Carcinoma of the Esophagus. Ann Surg Oncol 17, 634–642 (2010). https://doi.org/10.1245/s10434-009-0851-4

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  • DOI: https://doi.org/10.1245/s10434-009-0851-4

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