title: c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.
abstract: BACKGROUND
  c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients.
  
  
  METHODS
  The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines.
  
  
  RESULTS
  Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor.
  
  
  CONCLUSIONS
  The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. ozawa.youhei@opal.plala.or.jp.|Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. ozawa.youhei@opal.plala.or.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. yasu-naka@patholo2.med.tohoku.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
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 Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. felizola@med.tohoku.ac.jp.
authors.forename: Saulo J A
authors.initials: SJ
authors.lastname: Felizola
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. takeda.kenichirou@me.com.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. qq4b2ev9k@beach.ocn.ne.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. fafafapdx2000@yahoo.co.jp.|Department of Pathology, Tohoku University Hospital, Sendai, Japan. fafafapdx2000@yahoo.co.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. hirotaka_1106@yahoo.co.jp.|Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. hirotaka_1106@yahoo.co.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. supo4bowling9@yahoo.co.jp.|Department of Pathology, Tohoku University Hospital, Sendai, Japan. supo4bowling9@yahoo.co.jp.
authors.forename: Takuro
authors.initials: T
authors.lastname: Konno
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 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: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. miyata5@chuo-hp.jp.
authors.forename: Go
authors.initials: G
authors.lastname: Miyata
authors.affiliation: Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, 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
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. hsasano@patholo2.med.tohoku.ac.jp.|Department of Pathology, Tohoku University Hospital, Sendai, Japan. hsasano@patholo2.med.tohoku.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000077547:Crizotinib; D019610:Cytoprotection / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D010880:Piperidines / Q000494:pharmacology; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011720:Pyrazoles; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D012333:RNA, Messenger; D000077547:Crizotinib; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met