Media type: E-Article Title: Overexpression of TGF‐β1 in esophageal (Barrett's) adenocarcinoma is associated with advanced stage of disease and poor prognosis Contributor: von Rahden, Burkhard H. A.; Stein, Hubert J.; Feith, Marcus; Pühringer, Franziska; Theisen, Jörg; Siewert, J. Rüdiger; Sarbia, Mario imprint: Wiley, 2006 Published in: Molecular Carcinogenesis Language: English DOI: 10.1002/mc.20259 ISSN: 0899-1987; 1098-2744 Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Expression of TGF‐β1, a major member of the TGF‐β superfamily and important promoter of tumor growth, was investigated in a series of primary resected esophageal (Barrett's) adenocarcinomas to establish its potential clinical significance and prognostic relevance in this entity. A series of 123 primary resected adenocarcinomas of the distal esophagus, arising in association with Barrett's esophagus, and corresponding normal squamous epithelium (<jats:italic>n</jats:italic> = 12) and non‐malignant Barrett's mucosa (<jats:italic>n</jats:italic> = 11), were investigated by means of quantitative RT‐PCR for expression of <jats:italic>TGF‐β1</jats:italic>, using paraffin embedded tissue samples. Gene expression levels were correlated with clinical parameters and overall survival. <jats:italic>TGF‐β1</jats:italic> mRNA was expressed in all tumors, but relative gene expression levels varied largely among different tumors. The relative gene expression was significantly higher in tumor tissue compared to squamous epithelium (<jats:italic>P</jats:italic> = 0.005) and Barrett's mucosa (<jats:italic>P</jats:italic>=0.002), expressing only low amounts of <jats:italic>TGF‐β1</jats:italic>. Relative overexpression of the <jats:italic>TGF‐β1</jats:italic> gene was associated with advanced UICC stage (III/IV vs. I/II; <jats:italic>P</jats:italic> = 0.009), depth of tumor infiltration (pT3 vs. pT1/2; <jats:italic>P</jats:italic> < 0.001), nodal involvement (pN1 vs. pN0; <jats:italic>P</jats:italic> = 0.006), and lymphatic vessel invasion (L1 vs. L0; <jats:italic>P</jats:italic> = 0.011). On univariate survival analysis, <jats:italic>TGF‐β1</jats:italic> overexpression had a significant negative impact on survival (log rank test; <jats:italic>P</jats:italic> = 0.0255). However, the prognostic impact was not independent from other strong predictors of survival (pT, pN) on multivariate survival analysis. Our data show that <jats:italic>TGF‐β1</jats:italic> overexpression is associated with advanced stage of esophageal adenocarcinoma and implies a negative impact on survival. The TGF‐β pathway may be a potential target for molecular therapies of advanced tumors of this entity. © 2006 Wiley‐Liss, Inc.</jats:p>