Epithelial-mesenchymal transition in non-small cell lung cancer

Non-small cell lung carcinoma (NSCLC) is a highly fibrotic malignancy, which exhibits a prominent desmoplastic stroma. Epithelial-mesenchymal transition (EMT) is one of the main modes of carcinoma invasion. We identified the stromal N-glycoprotein periostin by mass spectrometry of lung adenocarcinoma pleural effusions. Validation on a NSCLC tissue microarray and on tumor whole sections by immunohistochemistry indicated that periostin is strongly upregulated at the invasive front in both tumor epithelia and the surrounding matricellular space. In comparison to collagen, elastin and vimentin, periostin was found to be most closely associated with parameters of tumor progression such as larger size and higher stage, with the squamous cell histotype, and with decreased survival. An association with decreased survival was also found for the cell adhesion molecule L1CAM. In conclusion, enlargement of NSCLC tumors is associated with an increase of desmoplastic stroma and concomitant upregulation of EMT markers at the invasive front. The tumor-stroma interface may be a candidate topographic region for stroma- or EMT-directed therapy.