Bronchioloalveolar adenocarcinoma of lung - Monoclonal origin for multifocal disease
Bronchioloalveolar adenocarcinoma of lung - Monoclonal origin for multifocal disease
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DOI：
10.1097/00000478-199811000-00004
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发表时间：
1998-11-01
影响因子：
5.6
通讯作者：
Yousem, SA
中科院分区：
文献类型：
--
作者：
Holst, VA;Finkelstein, S;Yousem, SA
为了了解多灶性细支气管肺泡癌（BAC）的组织发生和分子发病机制，我们采用拓扑基因分型方法对28例BAC病例进行了研究，检测K - ras外显子1突变和p53杂合性缺失（LOH）情况。这种分析方法显示，在孤立性BAC中12.5%存在K - ras外显子1突变，在有微观或宏观卫星病灶的BAC中40%存在该突变，在有胸腔内转移的BAC中60%存在该突变。在所有存在K - ras突变的病例中，原发灶、卫星灶和胸腔内转移灶都存在相同的点突变。当在原发灶中检测到p53 LOH时，在卫星灶和胸腔内转移灶中也能检测到。未发现K - ras突变与p53 LOH之间存在显著关联。这些结果有力地支持了多灶性BAC的单克隆起源。此外，这些发现支持了通过肺泡内播散途径、肺内淋巴管播散或气溶胶化导致在不同部位种植来解释多灶性BAC起源的理论。注意到与孤立性BAC相比，有卫星灶或转移灶的BAC中K - ras突变和p53 LOH的频率有增加的趋势。
In an attempt to understand the histogenesis and molecular pathogenesis of multifocal bronchioloalveolar lung carcinoma (BAC) we studied 28 cases of BAC using a topographic genotyping approach for the presence of K-ras exon 1 mutations and p53 loss of heterozygosity (LOH). This analytical approach demonstrated K-ras exon 1 mutations in 12.5% of solitary BACs, 40% of BACs with microscopic or macroscopic satellite lesions, and 60% of BACs with intrathoracic metastases. In all cases with K-rus mutations, the identical point mutation was present in the primary, satellite, and intrathoracic metastatic lesions. When p53 LOH was demonstrated in the primary lesion, it was also detected in the satellites and intrathoracic metastases. No significant association was noted between the presence of K-ras mutations and p53 LOH. The results strongly support a monoclonal origin of multifocal BACs. Furthermore, the findings support the theories explaining the origin of multifocal BAC by intraalveolar route of spread, intrapulmonary lymphatic spread, or aerosolization leading to implantation at different sites. A trend toward an increased frequency of K-rns mutations and p53 LOH in BACs with satellites or metastases compared to solitary BACs was noted.