Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer.
Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer.
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发表时间：
2000-05
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通讯作者：
Robert L. Keith;York E. Miller;R. Gemmill;H. A. Drabkin;Edward C. Dempsey;T. Kennedy;S. Prindiville;Wilbur A. Franklin
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作者：
Robert L. Keith;York E. Miller;R. Gemmill;H. A. Drabkin;Edward C. Dempsey;T. Kennedy;S. Prindiville;Wilbur A. Franklin
肺癌的发生被认为是一个多步骤的过程，但对侵袭性肺癌发生前的连续形态和分子变化的详细了解仍然难以捉摸。为了更好地了解早期肺癌的发生，我们启动了一项针对肺癌高危吸烟者的荧光支气管镜检查计划。在这些受试者的支气管活检中，我们观察到一种独特的病变，由与化生或发育不良的鳞状支气管壁上皮紧密并列并突入的毛细血管组成，即血管生成的鳞状异型增生(ASD)。毛细血管投射的连续切片证实它们代表粘膜内的毛细血管环。ASD的微血管密度高于正常黏膜(P=0.0003)，但与其他形式的增生或异型增生相比无显著差异。因此，ASD代表了一种定性的不同形式的血管生成，其中存在着毛细血管微血管的结构性重排。对随机亚组病变的表面上皮细胞的遗传分析显示，53%的ASD病变在染色体3p处丢失了杂合性。未发现确认的P53突变。与正常上皮相比，ASD皮损的增殖活性明显增强。无癌高危吸烟者158人中54人(34%)发生ASD，接受荧光支气管镜检查的10名鳞癌患者中有6人发生ASD。1例早期浸润性癌因ASD与浸润性肿瘤并存而值得注意。77例(59%)ASD病变仅通过异常荧光发现。初诊一年后，对11例患者的20个支气管处进行了再次活检。在这些部位中的9个(45%)，发现病变持续存在。在16名正常非吸烟者对照受试者的活检组织中没有发现这种病变。在高危吸烟者中出现这种损害表明，微血管的异常模式可能发生在支气管癌变的早期阶段。
Lung carcinogenesis is assumed to be a multistep process, but detailed understanding of the sequential morphological and molecular changes preceding invasive lung cancer remains elusive. To better understand early lung carcinogenesis, we initiated a program of fluorescence bronchoscopy in smokers at high risk for lung cancer. In the bronchial biopsies from these subjects, we observed a unique lesion consisting of capillary blood vessels closely juxtaposed to and projecting into metaplastic or dysplastic squamous bronchial epithelium, angiogenic squamous dysplasia (ASD). Serial sections of the capillary projections confirmed that they represent intramucosal capillary loops. Microvessel density in ASD was elevated in comparison to normal mucosa (P = 0.0003) but not in comparison to other forms of hyperplasia or dysplasia. ASD thus represents a qualitatively distinct form of angiogenesis in which there is architectural rearrangement of the capillary microvasculature. Genetic analysis of surface epithelium in a random subset of lesions revealed loss of heterozygosity at chromosome 3p in 53% of ASD lesions. No confirmed p53 mutations were identified. Compared with normal epithelium, proliferative activity was markedly elevated in ASD lesions. ASD occurred in 54 of 158 (34%) high-risk smokers without carcinoma and in 6 of 10 patients with squamous carcinoma who underwent fluorescence bronchoscopy. One early-stage invasive carcinoma was noteworthy for the occurrence of ASD juxtaposed to invasive tumor. Seventy-seven (59%) of the ASD lesions were detected by abnormal fluorescence alone. Twenty bronchial sites (11 patients) were rebiopsied 1 year after the initial diagnosis. At nine (45%) of these sites, the lesion was found to persist. The lesion was not present in biopsies from 16 normal nonsmoker control subjects. The presence of this lesion in high-risk smokers suggests that aberrant patterns of microvascularization may occur at an early stage of bronchial carcinogenesis.