CYFRA-21-1 ENZYME-LINKED-IMMUNOSORBENT-ASSAY - EVALUATION AS A TUMOR-MARKER IN NON-SMALL-CELL LUNG-CANCER

Background: The CYFRA 21-1, a newly developed sandwich enzyme-linked i mmunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its mali gnant counterpart. The present study was designed to investigate wheth er CYFRA 21-1 is a sensitive and specific tumor marker for non-small c ell lung cancer. Methods: CYFRA 21-1 assay, using two specific monoclo nal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 wa s also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. Results: The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, th e median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign p ulmonary disease, such as tuberculosis, pneumonia, or COPD. Using tile cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n = 74), adenocarcinoma (n = 54), undifferentiated large cell carcino ma (n = 11), and small cell lung cancer (n = 25) were 62%, 39%, 36%, a nd 20%, respectively. Despite the cell types, the sensitivities of CYF RA 21-1 in non-small cell lung cancer (NSCLC, n = 169) were 51% (CEA 4 2%, SCC 20%). The sensitivity of CEA was significantly higher in patie nts with adenocarcinoma (58%) than other markers; while in patients wi th squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivi ty. The median level of CYFRA 21-1 in squamous cell carcinoma is signi ficantly higher than that of other cell types (Mann-Whitney test, p<0. 001). The serum level and sensitivity of CYFRA 21-1 were well correlat ed with staging and tumor size in squamous cell carcinoma. The CYFRA 2 1-1 values were measured for monitoring progression of disease in 20 p atients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients,vith progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was ob served in patients with stabilized disease (p>0.1). Conclusion: For pa tients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 i s not only a sensitive and specific tumor marker, but also may be a us eful adjunctive marker for disease monitoring.