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


CONCLUSIONS
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.
Department of Surgery II, Osaka University Medical School, Japan.
K
K
Iihara
H
H
Shiozaki
H
H
Tahara
K
K
Kobayashi
M
M
Inoue
S
S
Tamura
M
M
Miyata
H
H
Oka
Y
Y
Doki
T
T
Mori
D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology; D002455:Cell Division; D066246:ErbB Receptors / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D016019:Survival Analysis; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors