Pulmonary Fibrosis and Carcinoma of the Lung : An Analysis of Genetic Abnormalities of Honeycombed Lesion and IPF-Related Lung Carcinoma.

肺纤维化和肺癌：蜂窝状病变和 IPF 相关肺癌的遗传异常分析。

基本信息

批准号：
09470054
负责人：
FUKAYAMA Masashi
金额：
$ 9.54万
依托单位：
The University of Tokyo (1999)Jichi Medical University (1997-1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

We investigated a mechanism underlying the high frequency of lung carcinomas in idiopathic pulmonary fibrosis (IPF). Firstly, the study of a clinico-pathologic features of IPF with lung carcinomas demonstrated that the carcinomas showed a topographically intimate relationship with the honeycombed legion in IPF. Second, the morphometry revealed that squamous metaplasia was significantly frequent among epithelial cell components of the honeycombed legions of IPF with lung carcinoma. However, the labeling indexes of Ki-67 and p53 or the gardes of cellular atypia in squamous metaplasia were not different in IPF with or without lung carcinomas. Since the pattern of genetic abnormalities might reflect the development process of a carcinoma, we evaluated FHIT gene abnormality by RT-PCR and methylation status of p16 promoter regions by bisulfite treatment and PCR. The frequency of methylation was significantly higher in IPF-related lung carcinomas, but was not observed in squamous metaplasia in IPF with lung carcinoma, the tissue of which was dissected directly from the slides. These results suggest that methylation of p16 is relatively a late event in the carcinogenesis in IPF, and that there might be some genetic basis commonly underlying squamous metaplasia and carcinoma in The IPF-patients with lung carcinomas. To evaluate this hypothesis, we investigated genetic polymorphism of the enzymes, which are involved in the processing of aromatic amines. As a result, a decreased ability type was significantly frequent in IPF without lung carcinomas, confirming that there might be a genetic basis for the high frequency of lung carcinomas in IPF. Future studies should focus on both aspects in IPF with lung carcinomas, genetic abnormalities in metaplastic epithelia of the honeycombed legion and genetic basis including polymorphism of DNA repair genes.

我们研究了一种在特发性肺纤维化（IPF）中肺癌高频的基础机制。首先，对IPF肺癌的临床病理特征的研究表明，癌显示了与IPF中蜂窝状军团的地形亲密关系。其次，形态学表明，在IPF的蜂窝状菌群中，鳞状化生的上皮细胞成分中有明显的频繁。然而，在有或没有肺癌的IPF中，Ki-67和p53的标签索引或鳞状化生中的细胞异常花园没有差异。由于遗传异常的模式可能反映了癌的发育过程，因此我们通过RT-PCR评估了FHIT基因异常，并通过Bisulfite治疗和PCR评估了P16启动子区域的甲基化状态。与IPF相关的肺癌中甲基化的频率明显更高，但在IPF的鳞状化生中未观察到肺癌，肺癌的组织直接从载玻片中解剖。这些结果表明，p16的甲基化是IPF癌发生中的一个晚期事件，并且可能存在某种遗传基础，通常存在肺癌IPF患者中的基础鳞状化生和癌。为了评估这一假设，我们研究了与芳香胺的加工有关的酶的遗传多态性。结果，在没有肺癌的情况下，IPF的能力类型显着频繁，证实IPF中肺癌高频可能存在遗传基础。未来的研究应侧重于IPF的两个方面，肺癌，蜂窝状军团的化生性上皮中的遗传异常和遗传基础，包括DNA修复基因的多态性。