Field Effect in Lung Carcinogenesis Associated with Pulmonary Fibrosis
T Fujii, A Miyamoto, K Kishi, K Yoshimura, K Ohashi. Toranomon Hospital, Tokyo, Japan; Okinaka Memorial Institute for Medical Research, Tokyo, Japan
Background: Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is associated with high prevalence of lung carcinogenesis especially in smokers, which is somewhat reminiscent of the hypercarcinogenic state in chronic hepatitis. To investigate the potential genetic or epigenetic changes in IPF/UIP, we performed microsatellite instability assay using mono- or tetranucleotide markers and methylation-specific polymerase chain reaction (PCR) on video-assisted thoracoscopic lung biopsies.
Design: Five video-assisted thoracoscopic lung biopsies of IPF/UIP were included in the present study. Genomic DNA was extracted from formalin fixed paraffin embedded tissue sections that were manually dissected for cancer, non-neoplastic lung tissue with or without UIP, and/or lymph node (if available). The presence or absence of microsatellite instability was assessed by fragment analysis on capillary electrophoresis using fluorescent labeled primers for mono- or tetra-nucleotide repeat markers, which included the following loci: NR21, BAT26, BAT25, NR24, UT5037, MYCL1, D9S303, D21S1436, D20S82 and D2S443. Lymph node or lung tissue with no or minimal fibrosis were regarded as normal for microsatellite analysis. The status of promoter CpG methylation was examined by methylation-specific PCR after bisulfite conversion using primers corresponding to the unmethylated and methylated alleles of the following genes: APC, ATM, CDKN2A, DAPK, ECAD, hMLH1, MGMT, RASSF1A, TGFBR2 and TCF21.
Results: No microsatellite instability was identified in four cases of IPF/UIP with/without associated lung cancer. DNA methylation was identified in four of five cases with IPF/UIP.
IP: pulmonary fibrosis; N: normal; T: tumor; U: unmethylaed; M: methylated; ND: not determined.
|1 (71/M)||IP ca(+)||N (lung)||U||U||U||U||U|
|2 (77/M)||IP ca(+)||N (lung)||U||U||ND||U||ND|
|T (squamous ca)||U||U||ND||U||ND|
|3 (69/M)||IP||IP (slight)||U||ND||ND||U||ND|
|4 (56/M)||IP||N (LN)||U||U||ND||ND||ND|
|5 (69/M)||IP||N (lung)||U||U||ND||ND||U|
Conclusions: The presence of epigenetic alteration (DNA CpG methylation) may be involved in lung carcinogenesis in pulmonary fibrosis in this preliminary study.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 250, Tuesday Afternoon