Expression of Transforming Growth Factor β1 and E-Cadherin Proteins in Pulmonary Adenocarcinoma: Its Significance in Tumor Progression

PURPOSE This study was conducted in order to investigate the significance of transforming growth factor β1 (TGFβ1) and E-cadherin proteins in tumor progression of lung adenocarcinoma and to evaluate their differential expression in association with morphologic characteristics. MATERIALS AND METHODS A total of 65 pulmonary adenocarcinomas were reclassified according to the new classification system proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. Tumor samples from 20 adenocarcinomas in situ (AIS, formerly bronchioloalveolar carcinoma [BAC]), 9 minimally invasive adenocarcinomas (MIA, formerly BAC with ≤ 5 mm invasion), 17 lepidic predominant adenocarcinomas (LPA, formerly mixed adenocarcinoma showing nonmucinous BAC features with >5 mm invasion), and 19 invasive adenocarcinomas with no BAC features were analyzed by immunohistochemistry for expression of TGFβ1 and E-cadherin proteins. RESULTS TGFβ1 expression was detected in 46% (21/46) of noninvasive elements and 87% (39/45) of invasive elements (p=0.001). E-Cadherin expression was less frequent in invasive components than in noninvasive components (38% vs. 65%, p=0.009). Negative correlation was identified between TGFβ1 expression and E-cadherin expression in noninvasive elements (p=0.022). More importantly, significantly higher frequency of TGFβ1 expression was observed in noninvasive components of LPA (14/17, 82%), compared with those of either AIS (5/20, 25%) or MIA (2/9, 22%) (p=0.008). CONCLUSION Our data indicate involvement of both TGFβ1 and E-cadherin proteins in tumor progression of pulmonary adenocarcinoma. It is noteworthy that TGFβ1 up-regulation precedes alveolar destruction by invasion of tumor cells. TGFβ1 may thus have the potential to improve lung adenocarcinoma diagnostics and therapeutics.