Subject(s)
Antineoplastic Agents/adverse effects , Lung Diseases, Interstitial/chemically induced , Piperazines/adverse effects , Pulmonary Alveoli/pathology , Pulmonary Eosinophilia/pathology , Pulmonary Fibrosis/pathology , Pyrimidines/adverse effects , Benzamides , Humans , Imatinib Mesylate , Lung Diseases, Interstitial/pathology , Male , Middle Aged , Protein-Tyrosine Kinases/antagonists & inhibitors , Pulmonary Eosinophilia/etiology , Pulmonary Fibrosis/etiologyABSTRACT
Hypermethylation of CpG island is a common mechanism by which tumor suppressor genes are inactivated. The tumor suppressor genes p16(INK4a) and p15(INK4b) are important components of the cell cycles. We have studied the feasibility of detecting tumor-associated aberrant p16(INK4a) and p15(INK4b) methylation in non-small cell lung cancer (NSCLC) using methylation-specific PCR. We found a high frequency of hypermethylation of the p16(INK4a) gene in 17 of 45 cases of NSCLC. In this study, there was no difference between the clinicopathological features or overall survival of patients with and without p16(INK4a) methylation. On the other hand, p15(INK4b) promoter hypermethylation is rare (5/45) in lung cancer and occurs in association with p16(INK4a) methylation. The overall survival of patients with p15(INK4b) methylation was markedly shortened in this series. We also analyzed cells in bronchial washings, and p16(INK4a) methylation was detected in 4 of 17 cases of NSCLC. Moreover, 1 of 10 plasma samples from patients with NSCLC was positive for p16(INK4a) methylation. Our results suggest a possible prognostic role of p15(INK4b) methylation in NSCLC, and that the detection of aberrant p16(INK4a) methylation in both bronchial washings and plasma may be useful for cancer diagnosis.
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Carrier Proteins/genetics , Cell Cycle Proteins , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Methylation , Lung Neoplasms/pathology , Tumor Suppressor Proteins , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/cytology , Carcinoma, Non-Small-Cell Lung/genetics , Cyclin-Dependent Kinase Inhibitor p15 , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Female , Humans , Lung Neoplasms/genetics , Male , Middle Aged , Neoplasm Staging , Promoter Regions, Genetic/genetics , Survival AnalysisABSTRACT
A newly approved oral fluoropyrimidine, TS-1, is a dihydropyrimide dehydrogenase (DPD)-inhibiting fluoropyrimidine (DIF) drug. We describe a case of interstitial pneumonia probably caused by TS-1. A peripheral blood lymphocytes stimulating test (DLST) with TS-1 demonstrated a substantial positive reaction. So far only three cases of TS-1-induced interstitial pneumonia have been reported but the relationship between interstitial pneumonia and TS-1 was demonstrated only in this case. Considering that interstitial pneumonia has also been reported with 5-FU, it is necessary in the future to clarify which component of this drug is directly related to interstitial pneumonia.
