Frequent genetic alterations at the microsatellite level in cytologic sputum samples of patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology associ ated with DNA damage and malignancy. Bronchogenic carcinoma is the cause of death in 10% to 13% of IPF patients. Microsatellite instability (MSI) and loss of heterozygosity (LOH) are frequently detected in cancers. If these g enetic alterations could be observed in IPF, they might explain the higher relative risk of lung cancer in this disease. We investigated the incidence of MSI and LOH in sputum cytologic specimens from 26 IPF patients and 26 h ealthy, matched subjects, using 10 highly polymorphic microsatellite marker s. The electrophoretic pattern of each specimen was compared with that of c orresponding peripheral blood. Thirteen (50%) patients showed genetic alter ations, consisting either of MSI or LOH. Five (19%) patients exhibited MSI and 10 (39%) exhibited LOH in at least one microsatellite marker. Three (12 %) patients showed LOH in more than one marker. None of the healthy subject s exhibited genetic alterations In the studied markers. No correlation was found between the detected genetic alterations and age, disease duration, b lood gases, or spirometric parameters of the patients, Our findings suggest that the genetic alterations that we studied are frequent in IPF, are appa rently unrelated to the severity of the disease, and may be related to tumo rigenesis.