title: Low PHLDA3 expression in oesophageal squamous cell carcinomas is associated with poor prognosis.
abstract: OBJECTIVE
  Patients with oesophageal squamous cell carcinoma (ESCC) have a poor prognosis. Akt has been associated with malignant potential in several cancers, including ESCC. Pleckstrin homology-like domain, family A, member 3 (PHLDA3) has been identified as a direct target gene of p53 and as a potent inhibitor of Akt activation. The present study investigated the role of PHLDA3 expression and its ability to predict prognosis in patients with ESCC who did not receive induction therapy.
  
  
  METHODS
  The intensity of PHLDA3 expression was immunohistochemically analyzed in tumor and adjacent normal tissue samples from 84 patients with ESCC, 22 who underwent endoscopic submucosal dissection and 62 who underwent thoracic oesophagectomy.
  
  
  RESULTS
  High expression of PHLDA3 was observed in 60 (71.4%) patients and low expression in 24 (28.6%). Cancer-specific (p=0.029) and disease-free (p<0.001) survival rates were significantly lower in the PHLDA3 low-than in the PHLDA3 high-expression group, and low PHLDA3 expression was an independent predictor of postoperative recurrence (relative risk (RR)=0.38; 95% confidence interval (CI)=0.166-0.78; p=0.0074).
  
  
  CONCLUSIONS
  Low PHLDA3 expression in ESCC may be predictive of tumor recurrence suggesting that Akt activation may be a therapeutic target in ESCCs.
authors: Department of Surgery 1, Dokkyo Medical University, Tochigi, Japan muroi-h@dokkyomed.ac.jp.
authors: Hiroto
authors: H
authors: Muroi
authors: Department of Surgery 1, Dokkyo Medical University, Tochigi, Japan.
authors: Masanobu
authors: M
authors: Nakajima
authors: Department of Surgery 1, Dokkyo Medical University, Tochigi, Japan.
authors: Hitoshi
authors: H
authors: Satomura
authors: Department of Surgery 1, Dokkyo Medical University, Tochigi, Japan.
authors: Masakazu
authors: M
authors: Takahashi
authors: Department of Surgery 1, Dokkyo Medical University, Tochigi, Japan.
authors: Satoru
authors: S
authors: Yamaguchi
authors: Department of Surgery 1, Dokkyo Medical University, Tochigi, Japan.
authors: Kinro
authors: K
authors: Sasaki
authors: Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan.
authors: Takehiko
authors: T
authors: Yokobori
authors: Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan.
authors: Tatsuya
authors: T
authors: Miyazaki
authors: Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan.
authors: Hiroyuki
authors: H
authors: Kuwano
authors: Department of Surgery 1, Dokkyo Medical University, Tochigi, Japan.
authors: Hiroyuki
authors: H
authors: Kato
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis
chemical_list: D009687:Nuclear Proteins; C109277:TSSC3 protein
keywords: Akt; Oesophageal cancer; PHLDA3; prognostic factor