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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Murine double minute 2 predicts response of advanced esophageal squamous cell carcinoma to definitive chemoradiotherapy

Authors: Hiroshi Okamoto, Fumiyoshi Fujishima, Takashi Kamei, Yasuhiro Nakamura, Yohei Ozawa, Go Miyata, Toru Nakano, Kazunori Katsura, Shigeo Abe, Yusuke Taniyama, Tadashi Sakurai, Jin Teshima, Makoto Hikage, Hironobu Sasano, Noriaki Ohuchi

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Definitive chemoradiotherapy (dCRT) has recently become one of the most effective therapies for the treatment of esophageal squamous cell carcinoma (ESCC). However, it is also true this treatment has not been effective in all patients. Therefore, it is very important to evaluate the surrogate marker of dCRT in order to improve clinical outcomes of patients with ESCC. On the other hand, our previous study had suggested that murine double minute 2 (MDM2) and p16 were associated with chemoradioresistance in ESCC.

Methods

We selected pretreatment biopsy specimens of ESCC patients from our prospective clinical study on dCRT. Seventy-nine cases histologically diagnosed as ESCC were used. We immunohistochemically investigated these specimens using antibodies against MDM2, p53, p16, and Ki-67.

Results

The patients included 68 males and 11 females with a mean age of 63.3 years. The number of patients in each clinical stage was as follows: 22 in c-Stage I; 17 in c-Stage II; and 40 in c-Stage III. cT, cN, and cStage were significantly more advanced in the Failure group (including patients with persistent and recurrent disease after dCRT) than in the complete response (CR) group (patients with persistent CR after dCRT). The clinical stage inversely correlated with the CR rate and the rescue rate after failure. The overall survival rate was significantly worse in the patients with advanced cT, cN, and cStage levels, and in the Failure group. MDM2 positivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.014). The number of patients with an absence of p16 immunoreactivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.010) but not in cStageI or cStageII. Moreover, the overall survival with a Ki-67 ≥ 33.7% was significantly better than that with <33.7% for patients in cStageIII (P = 0.024).

Conclusions

The results of this study suggested that MDM2 and p16 are predictive markers for chemoradioresistance in cStageIII ESCC and Ki-67 is a prognostic marker following dCRT in cStageIII ESCC. These issues could contribute to the formulation of treatment strategy for patients with advanced ESCC.
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Metadata
Title
Murine double minute 2 predicts response of advanced esophageal squamous cell carcinoma to definitive chemoradiotherapy
Authors
Hiroshi Okamoto
Fumiyoshi Fujishima
Takashi Kamei
Yasuhiro Nakamura
Yohei Ozawa
Go Miyata
Toru Nakano
Kazunori Katsura
Shigeo Abe
Yusuke Taniyama
Tadashi Sakurai
Jin Teshima
Makoto Hikage
Hironobu Sasano
Noriaki Ohuchi
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1222-0

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