High phosphorylated 4E-binding protein 1 expression after chemoradiotherapy is a predictor for locoregional recurrence and worse survival in esophageal squamous cell carcinoma patients

J Surg Oncol. 2012 Mar;105(3):288-92. doi: 10.1002/jso.22097. Epub 2011 Sep 19.

Abstract

Background: As a well-known pivotal factor of 4E-binding protein 1 (4E-BP1) in controlling cancer proliferation, high expression of its phosphorylated form (p-4E-BP1) has been reported to be associated with poor outcome in various human cancers without pretreated with chemoradiotherapy (CRT). However, no data is available regarding the implication of p-4E-BP1 expression after CRT. Therefore, we conducted this study.

Methods: The expression of p-4E-BP1 was semiquantitatively examined with immunohistochemical staining in 60 ypT1T2 esophageal squamous cell carcinoma (SCC) patients and verified by western blot analysis in representative cases. The impact of p-4E-BP1 expression intensity on cancer recurrence and survival was assessed in combination with clinical and pathological descriptors.

Result: The 5-year disease specific survival (DSS) rate of patients with high p-4E-BP1 expression was significantly lower than that of patients with lower p-4E-BP1 expression (5 year DSS: 58% vs. 8.6%, P = 0.00064). Furthermore, in a multivariate analysis by Cox regression model, high p-4E-BP1 expression was confirmed to be an independent prognostic factor (HR: 2.269; unfavorable, P = 0.024) for DSS, while lymph node (HR: 3.016; unfavorable, P = 0.005) was also significant prognostic factor. High p-4E-BP1 expression was specifically associated with locoregional recurrence (LR; P < 0.05). The locoregional control rate reached 97.1% in low p-4E-BP1 tumors.

Conclusion: High p-4E-BP1 expression after CRT is a predictor for LR and worse survival in esophageal SCC patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / therapy
  • Cell Cycle Proteins
  • Chemoradiotherapy*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / therapy
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Prognosis
  • Retrospective Studies

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins