Modulation of neoangiogenesis in bronchial preneoplastic lesions

We have previously demonstrated that vascular count significantly increases in the preneoplastic lesions of the bronchial tree, starting from very low levels in the normal epithelium to a significantly higher number of microv essels in moderate dysplastic lesions and ill situ carcinomas. Vascular end othelial growth factor (VEGF) protein expression has shown to be strictly a ssociated with neovascularization both in human cancer and in various type of preinvasive lesions. A number of studies have demonstrated that mutant p 53 is involved in the regulation of angiogenesis, and immunohistochemical d etection of the p53 protein is associated with p53 gene mutations. In this study we looked for possible correlation between p53 protein detection, VEG F expression and vascular count in a series of preneoplastic and neoplastic lesions of the bronchial tree in order to investigate the angiogenic patte rn and its genetic control in the early steps of bronchial cancer developme nt. Twenty-four retrospective bronchial lesions with different grades of dy splasia and a case of normal bronchial epithelium were analysed. Surgical s pecimens removed from patients either confirmed, or suspect for lung carcin oma were stained immunohistochemically for CD34, VEGF, and p53. There were significant increases in microvascular density (MVD), VEGF, and p53 express ion from normal bronchial epithelium through moderate dysplasia to in situ carcinoma to invasive cancer and these factors were significantly associate d with moderate dysplastic lesions. A statistically significant difference was observed in MVD between hyperplastic-metaplastic, moderate dysplastic l esions and in situ carcinoma. A similar pattern was also observed for VEGF and p53 protein expression but no significant difference was observed betwe en moderate dysplastic lesions and in situ carcinoma with regard to VEGF pr otein expression. The association between MVD, VEGF expression, p53 mutatio ns and preinvasive lesions of the bronchial tree suggests that neoangiogene sis is 'switched' early in nonsmall cell lung cancer (NSCLC) development an d that p53 may have an important role in promoting angiogenesis in this hum an model of carcinogenesis.