Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma

Abstract

Transforming growth factor-beta (TGF-beta) inhibits epithelial cell proliferation. Inactivation of the TGF-beta signaling pathway is thought to play a role in tumorigenesis. Our purpose was to clarify the correlation between TGF-beta receptors or TGF-beta 1 expression and the clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for TGF-beta type I receptor (TGF-beta R-I), TGF-beta R-II and TGF-beta 1 was performed on surgical specimens obtained from 80 patients with esophageal SCC. Preoperative plasma TGF-beta1 levels were measured and correlated with pathologic features and clinical outcomes. Expression of TGF-beta R-I and TGF-beta R-II was reduced in 43 (53.8%) and 23 (28.8%) specimens, respectively. TGF-beta 1 was overexpressed in 29 (36.3%). Reduced expression of TGF-beta R-I and TGF-beta R-II showed a significant association with depth of invasion (p = 0.0015 and p = 0.0012), lymph node metastasis (p = 0.0309 and p = 0.0059) and pathologic stage (p = 0.0103 and p = 0.0401). Overexpression of TGF-beta 1 had a significant association with depth of invasion only (p = 0.0335). Reduced expression of TGF-beta R-I and TGF-beta R-II was correlated with cancer-specific survival (p = 0.0324 and p = 0.0243). The mean preoperative plasma TGF-beta 1 level was 10.5 +/- 0.8 ng/ml in patients with esophageal carcinoma and was significantly higher compared to healthy controls (p < 0.01). We demonstrate that reduced expression of TGF-beta receptors in esophageal SCC appears to be correlated with depth of invasion, lymph node metastasis, pathologic stage and poor prognosis. TGF-beta receptor expression may play a key role in the progression of this cancer.