Expression of Transforming Growth Factor beta1 and Cadherins in Lung Adenocarcinoma

ABSTRACT

PURPOSE: There is evidence supporting the concept of tumor progression from pulmonary adenocarcinoma in situ (formerly bronchioloalveolar carcinoma, BAC) to adenocarcinoma with varying degrees of invasion. The aim of this study was to investigate the role of transforming growth factor beta1 (TGFbeta1) in tumor invasiveness in lung adenocarcinoma, and to determine the potential relationships between its expression and immunophenotypes of cell adhesion molecules. MATERIALS AND METHODS: Tumor samples from adenocarcinoma in situ (n=13), minimally invasive adenocarcinoma (formerly BAC with 5 mm invasion, n=25) were examined for the expression of TGFbeta1, E-cadherin, N-cadherin, and H-cadherin proteins using immunohistochemistry. RESULTS: Of a total of 40 cases, 25 (63%) were positive for TGFbeta1. The frequency of immunoreactivity in patients with adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma was 23% (3/13), 50% (1/2), and 84% (21/25), respectively (p=0.001). TGFbeta1 correlated with T classification (p=0.006) and stage (p=0.001). Loss of E-cadherin expression was more frequently observed in invasive adenocarcinomas than in adenocarcinomas in situ (p=0.034). E-cadherin expression inversely correlated with T classification (p=0.009). TGFbeta1 expression showed a statistically significant correlation with H-cadherin expression (p=0.040), but not with E-cadherin expression (p=0.752). CONCLUSION: These results suggest that TGFbeta1 and E-cadherin may play an important role in invasive progression of lung adenocarcinoma through regulating epithelial-to-mesenchymal transition.