Cytokeratin 19 Fragment in Patients With Nonmalignant Respiratory Diseases

Study objective Cytokeratin 19 fragment (CYFRA) is a specific tumor marker in patients with lung cancer; however, it has been reported that serum CYFRA levels are elevated in some patients with nonmalignant respiratory diseases such as interstitial pulmonary fibrosis (IPF) and collagen disease-associated pulmonary fibrosis (CDPF). To investigate the serum CYFRA levels in nonmalignant respiratory diseases in detail, we studied 413 patients with respiratory diseases. Design Retrospective study. Setting University hospital. Patients Four hundred thirteen patients with nonmalignant respiratory diseases and lung cancer. Measurements and results Serum CYFRA levels were measured with a commercially available enzyme immunoassay kit. Immunohistochemical study was performed using monoclonal antibody Ks 19.1 (Rosch Diagnosica; Bern, Switzerland) on surgically resected or autopsied lung specimens. Gel electrophoresis and immunoblotting was performed with serum samples. In 149 patients with nonmalignant diseases except IPF and CDPF, the ratio of patients with > 3.5 ng/mL of serum CYFRA was 13.4%. In 13 of 30 patients (43.3%) with IPF and CDPF, the serum CYFRA levels were abnormally elevated. The 95th percentile serum CYFRA level of the patients with nonmalignant respiratory diseases was 6.2 ng/mL, and none of them had CYFRA levels > 20.3 ng/mL. Survival in patients with IPF and CDPF with elevated serum CYFRA levels were significantly lower than in those with normal range (p = 0.0335). Western blotting using serum from nonmalignant lung diseases and patients with lung cancer showed no apparent difference between them. An immunohistochemical study indicated CYFRA was selectively expressed in the pulmonary epithelial cells that covered the remodeling alveolar septi in nonmalignant respiratory disease. Conclusion Serum CYFRA was elevated in some nonmalignant respiratory diseases, especially in IPF and CDPF. The value of serum CYFRA would reflect the severity of lung injury in nonmalignant respiratory diseases and might be related to the prognosis in patients with IPF and CDPF.