Evaluation of Cytokeratin 19 Serum Fragments (Cyfra 21–1) in Patients with Lung Cancer: Results of a Multicenter Trial

Abstract

Recently, a new immunometric assay (Cyfra 21–1) was developed to measure serum concentrations of a soluble fragment of cytokeratin subunit 19. With this method, supplied by Boehringer Mannheim (EIA Test Cyfra 21–1), an Italian multicenter trial was performed in patients with lung cancer. Cyfra 21–1 serum levels were determined in 568 normal subjects (blood donors), 607 patients with non-malignant diseases (491 respiratory diseases) and 730 patients with malignancies. In the latter group 584 had lung cancer. All these 584 patients had pathologically confirmed disease; 314 were epidermoid tumors, 166 adenocarcinomas, 88 small cell cancers and 16 large cell cancers. In the 568 healthy blood donors the mean Cyfra 21–1 value was 0.91 ng/ml (SD 0.47 ng/ml; range 0.05–2.90 ng/ml). A threshold of 1.9 ng/ml was chosen as the upper limit of normality. High levels of Cyfra21–1 were observed in patients with chronic hepatitis (positivity rate: 17/51–33.3%) and with pancreatitis (positivity rate 5/16 - 31.3%). In 114 out of 491 (23.2%) patients with respiratory diseases Cyfra 21–1 showed values greater than 1.9 ng/ml. The overall sensitivity (all stages) of Cyfra 21–1 in lung cancer was 65.6% (383/584). When the histology was considered the highest positivity rates were found in patients with squamous cell tumors (226/314; 72%) followed by adenocarcinomas (105/166; 63%). In patients with SCLC the global sensitivity was 52.3% (46/88). Higher sensitivity of Cyfra 21–1 was observed from stage I to stage IV (53.9% vs 85.7%; Chisquare: p < 0.01). When comparing patients in whom curative resections were possible (up to stage IIIa) with patients suffering from inoperable tumors, a significant difference in Cyfra 21–1 positivies was found (59% vs 81.5%; Chi square p < 0.01).