Angiogenic Squamous Dysplasia as a Biomarker to Predict Progression to Lung Cancer

Angiogenic squamous dysplasia(ASD) is a term that has been introduced to describe a neoangiogenesis seen in bronchial dysplasias. One of many important angiogenic cytokines are the VEGFs. The VEGFs and their receptors are prime regulators of both physiological and pathological angiogenesis. But it is not clear whether ASD demonstrates the angiogenic switch or not, what is the mechanism of ASD. In this study, Immunohistochemical studies showed an expression of vascular endothelial growth factor in dysplastic bronchial epithelium. VEGF in the dysplastic cells in preneoplastic epithelium was observed in twenty-nine of 31 patients with ASD(93.5%), indicating that angiogenic switch occurred in early preneoplastic lesion including hyperplasia, metaplasia. ASD lesions were not identified in patients with COPD, whereas in 31 of 90 (34.4%) patients with squamous carcinoma, ASD was evident. In addition, the incidence of ASD increased as the hisotogical grade of preneoplastic lesion advanced, suggesting that the ASD may be a direct precursor lesion(P = 0.03). The author followed LIP the biologic behavior of dysplasia with respect to the status of ASD. There were significant associations between histological outcome and ASD status during the follow-up period(P = 0.04). These results suggested that ASD be used as biomarkers; to predict which dysplasias will progress to squamous cell carcinoma. Macrophages were identified in all(100%) tumor stroma and ASDs. The number of macrophage beneath ASD was significantly higher than that beneath other abnormal epithelium. In addition, the number of macrophages beneath ASD was significantly correlated with the Count of microvessels beneath ASD. The results of the present study Suggested that Angiogenic squamous dyplasia(ASD) may represent ail precursor of lung cancer and may serve as ail useful intermediate pathologic biomarker for early detection of lung cancer and chemoprevention. Macrophage beneath ASD may play ail important role in early angiogenesis of ASD.