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

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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.