BACKGROUND: Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia such as respiratory epithelial cells and their malignant counterparts. An immu- noradiometric assay is available to detect a fragment of the cytokeratin, referred to as Cyfra 21-1 in the serum. This study was conducted to evaluate the clinical utility of this new marker in the diagnosis of lung cancer compared with established markers of squamous cell carcinoma antigen (SCC Ag) and carcino-embryonic antigen(CEA). In addition, we compared the diagnostic sensitivity and specificity of Cyfra 21-1 with those of SCC Ag in squamous cell carcinoma of the lung. We also measured the level of Cyfra 21-1 in the different stages of squamous cell carcinoma of the lung. METHOD: We measured Cyfra 21-1(ELSA-CYFRA 21-1), SCC Ag(ABBOTT SCC RIABEAD) and CEA(ELSA2-CEA) in 79 patients with primary lung cancer and in 78 persons as a comparison group including 32 patients with pulmonary tuberculosis, 23 patients with benign lung disease and 23 cases with healthy individual. Cyfra 21-1 is measured by a solid-phase immunoradiometric assay(CIS Bio International, France) based on the two-site sandwich method. SCC Ag is measured by a radioimmunoassay (Abbott Laboratories, USA). CEA is measured by a immunoradiometric assay(CIS Bio International, France). All data were expressed as the mean+/-standard deviation. RESULTS: 1) The mean value of Cyfra 21-1 was 18.38+/-3.65 ng/mL in the lung cancer and 1.16+/-0.53 ng/mL in the comparison group(p<0.0001). SCC Ag was 3.53+/-6.06 ng/mL in the lung cancer and 1.19+/-0.5 ng/mL in the comparison group(p<0.01). CEA was 35.03+/-13.9 ng/mL in the lung cancer and 2.89+/-1.01 ng/mL in the comparison group(p<0.0001). 2) Cyfra 21-1 level in squamous cell carcinoma(31.52+/-40.13 ng/mL) was higher than that in adenocarcinoma(2.41+/-1.34 ng/mL)(p<0.0001) and small cell carcinoma(2.15+/-2.05 ng/mL)(p= 0.007). SCC Ag level in squamous cell carcinoma(5.1 +/-7.68 ng/mL) was higher than that in adenocarcinoma(1.36+/-0.69 ng/mL)(p=0.009) and small cell carcinoma/1.1 +/-0.24 ng/mL) (p=0.024). 3) The level of Cyfra 21-1 was not correlated with the progression of stage in squamous cell carcinoma of the lung. 4) Using the cut-off value of 3.3ng/mL, the diagnostic sensitivity of Cyfra 21-1 was 83% in squamous cell carcinoma, 22% in adenocarcinoma and 17% in small cell carcinoma. The sensitivity of SCC Ag and CEA were 39% and 20%, respectively in squamous cell carcinoma, 11% and 39% in adenocarcinoma, and 0% and 33% in small cell carcinoma. 5) Comparison of the receiver operating characteristics curves(ROC curve) for Cyfra 21-1, SCC Ag and CEA revealed that Cyfra 21-1 showed highest diagnostic sensitivity among them in the diagnosis of lung cancer. CONCLUSION: Cyfra 21-1 is thought to be a better tumor marker for the diagnosis of lung cancer than SCC Ag and CEA, especially in squamous cell carcinoma of the lung.