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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.

我们研究了特发性肺纤维化（IPF）中肺癌发生率高的机制。首先，对伴有肺癌的IPF的临床病理特征的研究表明，肺癌与IPF中的蜂窝军团在地形学上表现出密切的关系。其次，形态测定显示，鳞状上皮化生在伴有肺癌的IPF蜂窝状军团的上皮细胞成分中显著频繁。而在IPF伴或不伴肺癌组中，Ki-67、p53的标记指数及鳞状上皮化生的细胞计数无明显差异。由于遗传异常的模式可能反映了癌症的发展过程，我们通过RT-PCR和亚硫酸氢盐处理和PCR的p16启动子区域的甲基化状态来评估FHIT基因异常。甲基化的频率在IPF相关肺癌中显著更高，但在IPF伴肺癌的鳞状化生中未观察到，其组织直接从载玻片上解剖。这些结果表明，p16甲基化在IPF的癌变过程中是一个相对较晚的事件，并且可能存在一些遗传基础，这些遗传基础通常是IPF肺癌患者鳞状上皮化生和癌的基础。为了评估这一假设，我们研究了参与芳香胺加工的酶的遗传多态性。因此，能力下降型在无肺癌的IPF中显著频繁，证实IPF中肺癌的高频率可能有遗传基础。未来的研究应集中在两个方面的IPF与肺癌，在化生上皮细胞的蜂窝军团的遗传异常和遗传基础，包括DNA修复基因的多态性。