Prognostic significance of transforming growth factor-alpha in human esophageal carcinoma. Implication for the autocrine proliferation

Cancer. 1993 May 15;71(10):2902-9. doi: 10.1002/1097-0142(19930515)71:10<2902::aid-cncr2820711004>;2-j.


Background: The authors recently used immunostaining to demonstrate that patients with epidermal growth factor receptor (EGFR) overexpression have poor survival after surgery. However, the clinical significance of transforming growth factor (TGF)-alpha, one of the ligands of EGFR, has not been demonstrated in esophageal carcinoma.

Methods: Immunohistochemical study for TGF-alpha and EGFR was performed on 57 esophageal squamous cell carcinomas using monoclonal antibodies.

Results: TGF-alpha expression was positive in 35% of the tumors, and EGFR overexpression, defined as stronger staining in cancer cells than in normal epithelium, was positive in 43% of the tumors, according to the authors' arbitrary criteria. The incidence of TGF-alpha positivity was relatively higher in patients with the EGFR overexpression (EGFR+) than in the patients with non-overexpression (EGFR-). The survival rate was significantly lower in patients with TGF-alpha(+) than in those with TGF-alpha(-) (P < 0.01) and in patients with EGFR(+) than in patients with EGFR(-) (P < 0.01), respectively. Considering TGF-alpha and EGFR expression simultaneously, the survival rate of the patients with TGF-alpha(+)/EGFR(+) tumors was the lowest of the four subgroups, with statistically significant differences noted. These relationships between the immunoreactivities and survival curves were observed in the analysis within patients with node-positive disease. In addition, a multivariate statistical analysis demonstrated that TGF-alpha was the only significant variable, whereas EGFR and nodal status provided no additional information regarding postoperative survival.

Conclusion: The results presented suggest that TGF-alpha may act as an autocrine growth factor through hyperproducing EGFR and that its expression and EGFR overexpression may prove useful as a valuable prognostic indicator for patients with esophageal carcinoma.

MeSH terms

  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / pathology
  • Cell Division
  • ErbB Receptors / metabolism*
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Multivariate Analysis
  • Prognosis
  • Survival Analysis
  • Transforming Growth Factor alpha / metabolism*


  • Transforming Growth Factor alpha
  • ErbB Receptors