Low PHLDA3 expression in oesophageal squamous cell carcinomas is associated with poor prognosis

Anticancer Res. 2015 Feb;35(2):949-54.


Background/aim: 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.

Materials and 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).

Conclusion: Low PHLDA3 expression in ESCC may be predictive of tumor recurrence suggesting that Akt activation may be a therapeutic target in ESCCs.

Keywords: Akt; Oesophageal cancer; PHLDA3; prognostic factor.

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Esophageal Neoplasms / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Prognosis


  • Nuclear Proteins
  • TSSC3 protein