title: Murine double minute 2 predicts response of advanced esophageal squamous cell carcinoma to definitive chemoradiotherapy.
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.
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. hi-ok-0531@med.tohoku.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai, Japan. ffujishima@patholo2.med.tohoku.ac.jp.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Fujishima
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. tkamei@med.tohoku.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamei
authors.affiliation: Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan. yasu-naka@patholo2.med.tohoku.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. ozawa.youhei@opal.plala.or.jp.|Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan. ozawa.youhei@opal.plala.or.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. miyata5@med.tohoku.ac.jp.
authors.forename: Go
authors.initials: G
authors.lastname: Miyata
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. torun@med.tohoku.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. k2azunori@msn.com.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Katsura
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. s-abey43@wg8.so-net.ne.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. yusuketaniyama@med.tohoku.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Taniyama
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. tsakurai@med.tohoku.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. jintesshy@yahoo.co.jp.
authors.forename: Jin
authors.initials: J
authors.lastname: Teshima
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. mhikage@med.tohoku.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hikage
authors.affiliation: Department of Pathology, Tohoku University Hospital, Sendai, Japan. hsasano@patholo2.med.tohoku.ac.jp.|Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan. hsasano@patholo2.med.tohoku.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.affiliation: Department of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. noriaki-ohuchi@med.tohoku.ac.jp.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D012372:ROC Curve; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D051736:Proto-Oncogene Proteins c-mdm2