Abstract
Transforming growth factor‐β (TGF‐β) inhibits epithelial cell proliferation. Inactivation of the TGF‐β signaling pathway is thought to play a role in tumorigenesis. Our purpose was to clarify the correlation between TGF‐β receptors or TGF‐β1 expression and the clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). Immunohistochemical staining for TGF‐β type I receptor (TGF‐βR‐I), TGF‐βR‐II and TGF‐β1 was performed on surgical specimens obtained from 80 patients with esophageal SCC. Preoperative plasma TGF‐β1 levels were measured and correlated with pathologic features and clinical outcomes. Expression of TGF‐βR‐I and TGF‐βR‐II was reduced in 43 (53.8%) and 23 (28.8%) specimens, respectively. TGF‐β1 was overexpressed in 29 (36.3%). Reduced expression of TGF‐βR‐I and TGF‐βR‐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‐β1 had a significant association with depth of invasion only (p = 0.0335). Reduced expression of TGF‐βR‐I and TGF‐βR‐II was correlated with cancer‐specific survival (p = 0.0324 and p = 0.0243). The mean preoperative plasma TGF‐β1 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‐β receptors in esophageal SCC appears to be correlated with depth of invasion, lymph node metastasis, pathologic stage and poor prognosis. TGF‐β receptor expression may play a key role in the progression of this cancer. © 2003 Wiley‐Liss, Inc.