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.

[1]  David A. Lynch,et al.  Idiopathic pulmonary fibrosis: Diagnosis and treatment: International Consensus Statement , 2000 .

[2]  J. Fujita,et al.  Elevated serum and BAL cytokeratin 19 fragment in pulmonary fibrosis and acute interstitial pneumonia. , 1999, The European respiratory journal.

[3]  H. Satoh,et al.  Lung cancer cell line producing cytokeratin 19 fragment and sialyl Lewis X-i antigen. , 1998, Anticancer research.

[4]  M. Suga,et al.  ALTERATIONS IN CYTOKERATIN EXPRESSION BY THE ALVEOLAR LINING EPITHELIAL CELLS IN LUNG TISSUES FROM PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS , 1997, The Journal of pathology.

[5]  C. Mountain,et al.  Revisions in the International System for Staging Lung Cancer. , 1997, Chest.

[6]  H. Saito,et al.  Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases--a specific marker for bronchial epithelial injury. , 1997, American journal of respiratory and critical care medicine.

[7]  Y. Nagasaka,et al.  Assessment of serum CYFRA 21‐1 in lung cancer , 1996, Cancer.

[8]  N. Lai,et al.  CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer. , 1996, Chest.

[9]  H. Kato,et al.  Clinical Usefulness of CYFRA Assay in Diagnosing Lung Cancer: Measurement of Serum Cytokeratin Fragment , 1994, Japanese journal of cancer research : Gann.

[10]  P M Steinert,et al.  Structure, function, and dynamics of keratin intermediate filaments. , 1993, The Journal of investigative dermatology.

[11]  K. Partanen,et al.  Receiver operating characteristic (ROC) curve analysis of the tumour markers CEA, CA 50 and CA 242 in pancreatic cancer; results from a prospective study. , 1993, British Journal of Cancer.

[12]  D. Isenberg,et al.  Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. , 1993, Arthritis and rheumatism.

[13]  P. Coulombe,et al.  The cellular and molecular biology of keratins: beginning a new era. , 1993, Current opinion in cell biology.

[14]  J. Daurès,et al.  Serum fragment of cytokeratin subunit 19 measured by CYFRA 21-1 immunoradiometric assay as a marker of lung cancer. , 1993, Cancer research.

[15]  F. Arnett.  Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[16]  E. Fuchs.  Keratins as biochemical markers of epithelial differentiation. , 1988, Trends in genetics : TIG.

[17]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[18]  R. Kasukawa.  Preliminary diagnostic criteria for classification of mixed connective tissue disease , 1987 .

[19]  Benjamin Geiger,et al.  The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells , 1982, Cell.

[20]  A. Masi.  Preliminary criteria for the classification of systemic sclerosis (scleroderma). , 1980, Bulletin on the rheumatic diseases.

[21]  A. Bohan,et al.  Polymyositis and dermatomyositis (second of two parts). , 1975 .

[22]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.