Clinical and prognostic significance of tumor markers cytokeratin 19 fragment, carcinoembryonic antigen, and neuron-specific enolase in lung cancer

Marius Žemaitis¹, Raimundas Sakalauskas², Kęstutis Malakauskas^{1, 2}, Thomas Muley³, Jürgen Richard Fischer⁴, Harald Lahm⁵

¹Institute for Biomedical Research, ²Clinic of Pulmonology and Immunology, Kaunas University of Medicine, Lithuania, ³Department of Surgery, Thoraxklinik Heidelberg, University of Heidelberg, ⁴Klinik Löwenstein, ⁵Laboratory of Immunology and Molecular Biology, Thoraxklinik Heidelberg, University of Heidelberg, Germany

Key words: lung cancer, tumor markers, cytokeratin 19 fragment, carcinoembryonic antigen, neuron-specific enolase, prognostic factors.

Summary. Objective. To evaluate the clinical and prognostic significance of the tumor markers cytokeratin 19 fragment, carcinoembryonic antigen and neuron-specific enolase in lung cancer patients.

Materials and methods. Serum levels of cytokeratin 19 fragment, carcinoembryonic antigen and neuron-specific enolase were measured using electrochemical luminescence immunoassay in 46 lung cancer patients. Serum levels of cytokeratin 19 fragment, carcinoembryonic antigen, and neuron-specific enolase higher than 3.6 ng/ml, 5.0 ng/ml and 13.0 ng/ml, respectively, were considered as elevated.

Results. Cytokeratin 19 fragment, carcinoembryonic antigen, and neuron-specific enolase were elevated in 19.6%, 43.5%, and 63% of patients, respectively. Elevated levels of neuron-specific enolase were detected more frequently in smokers than in ex-smokers (p=0.003). Likewise preoperative levels of carcinoembryonic antigen (p=0.023) and neuron-specific enolase (p=0.007) were statistically higher in smokers than in ex-smokers. A significant correlation was detected between the level of cytokeratin 19 fragments and smoking cumulative exposure (r=0.542, p=0.037). The number of patients with elevated levels of cytokeratin 19 fragment and neuron-specific enolase was higher in more advanced disease than in early lung cancer (p=0.036 and p=0.036, respectively). Preoperative levels of cytokeratin 19 fragment (p=0.017 and p=0.016, respectively) and neuron-specific enolase (p=0.03 and p=0.006, respectively) were significantly associated with more advanced disease and tumor size, as well as tumor histology in non-small cell lung cancer (p=0.03 and p=0.016, respectively). Preoperative levels of cytokeratin 19 fragments were higher in squamous cell carcinoma than in adenocarcinoma (p=0.026). Elevated preoperative serum levels of cytokeratin 19 fragment predict a poor prognosis for lung cancer patients (p=0.007).

Conclusion. Alteration of serum tumor markers cytokeratin 19 fragment, carcinoembryonic antigen and neuron-specific enolase is associated with particular tumor histology, smoking habit, more advanced disease and poor prognosis.

Correspondence to M. Žemaitis, Clinic of Pulmonology and Immunology, Kaunas University of Medicine, Eivenių 2, 50009 Kaunas, Lithuania. E-mail: mzemaiti@kmu.lt

Received 23 February 2005, accepted 22 June 2005