Modulation of neoangiogenesis in bronchial preneoplastic lesions.
Modulation of neoangiogenesis in bronchial preneoplastic lesions.
复制标题
调节支气管癌前病变中的新血管生成。
DOI：
10.3892/or.6.4.813
复制
发表时间：
1999
期刊：
影响因子：
4.2
通讯作者：
F. Basolo
中科院分区：
文献类型：
--
作者：
G. Fontanini;A. Calcinai;L. Boldrini;M. Lucchi;A. Mussi;C. Angeletti;C. Cagno;M. Tognetti;F. Basolo
我们先前已经证明，在支气管树的癌前病变中，血管计数显著增加，从正常上皮中非常低的水平开始，到中度异常增生病变和原位癌中微血管数量的显著增加。血管内皮生长因子(VEGF)蛋白的表达已被证明与人类癌症和各种类型的侵袭前病变中的新生血管密切相关。大量研究表明突变型P53参与了血管生成的调控，免疫组织化学检测P53蛋白与P53基因突变有关。本研究通过对一系列癌前病变和癌变病变组织中P53蛋白检测、血管内皮生长因子表达与血管计数的相关性研究，探讨肺癌发生发展早期的血管生成模式及其遗传调控。对24例不同程度异型增生的支气管病变和1例正常支气管上皮进行了回顾性分析。对确诊或疑似肺癌患者的手术标本进行CD34、VEGF和P53免疫组织化学染色。在正常支气管上皮、中度不典型增生、原位癌、浸润性癌组织中，微血管密度(MVD)、血管内皮生长因子(VEGF)和P53的表达均显著升高，这些因素与中度不典型增生病变显著相关。MVD在增生化生、中度不典型增生和原位癌之间差异有统计学意义。VEGF和P53蛋白的表达也有相似的模式，但在中度异常增生性皮损和原位癌中的表达没有明显差异。微血管密度、血管内皮生长因子表达、P53突变与支气管树侵袭前病变之间的关系表明，新血管生成在非小细胞肺癌(NSCLC)发展的早期，P53可能在促进这一人类癌变模型中的血管生成中发挥重要作用。
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 microvessels in moderate dysplastic lesions and in situ carcinomas. Vascular endothelial growth factor (VEGF) protein expression has shown to be strictly associated with neovascularization both in human cancer and in various type of preinvasive lesions. A number of studies have demonstrated that mutant p53 is involved in the regulation of angiogenesis, and immunohistochemical detection of the p53 protein is associated with p53 gene mutations. In this study we looked for possible correlation between p53 protein detection, VEGF expression and vascular count in a series of preneoplastic and neoplastic lesions of the bronchial tree in order to investigate the angiogenic pattern and its genetic control in the early steps of bronchial cancer development. Twenty-four retrospective bronchial lesions with different grades of dysplasia and a case of normal bronchial epithelium were analysed. Surgical specimens removed from patients either confirmed, or suspect for lung carcinoma were stained immunohistochemically for CD34, VEGF, and p53. There were significant increases in microvascular density (MVD), VEGF, and p53 expression from normal bronchial epithelium through moderate dysplasia to in situ carcinoma to invasive cancer and these factors were significantly associated with moderate dysplastic lesions. A statistically significant difference was observed in MVD between hyperplastic-metaplastic, moderate dysplastic lesions and in situ carcinoma. A similar pattern was also observed for VEGF and p53 protein expression but no significant difference was observed between moderate dysplastic lesions and in situ carcinoma with regard to VEGF protein expression. The association between MVD, VEGF expression, p53 mutations and preinvasive lesions of the bronchial tree suggests that neoangiogenesis is early in non-small cell lung cancer (NSCLC) development and that p53 may have an important role in promoting angiogenesis in this human model of carcinogenesis.