The use of soluble cytokeratin fragments in the diagnosis of liver metastases.


Authors: M. Špišáková 1;  R. Kučera 1;  O. Topolčan 1;  M. Šafanda 1;  D. Slouka 1;  J. Kinkorová 1;  V. Třeška 2
Authors‘ workplace: Imunoanalytická laboratoř, FN a LF v Plzni, Univerzita Karlova v Praze 1;  Chirurgická klinika, FN a LF v Plzni, Univerzita Karlova v Praze 2
Published in: Klin. Biochem. Metab., 23 (44), 2015, No. 3, p. 95-99

Overview

Objective:
Monitoring and evaluation of benefit of the soluble cytokeratin fragments determination for the liver metastases diagnostics.

Design:
Combined retrospective and prospective study.

Material and Methods:
In the period from January 2010 to December 2014 was in the Laboratory of immunoanalysis examined 1616 serum samples of patients from lung and surgery clinic. Patients were divided into groups according to the diagnoses. C34 consisted of the patients with lung cancer in stage I, II and III. C787 group consisted of patients with metastatic liver disease without distinguishing of origin of these metastases. The control group consisted of patients treated for inflammatory lung diseases and then from patients who were treated for thyroid disorders or metabolic disorders. At the time of sample collection all the patients were in the compensated status. MonoTotal, CYFRA 21-1 and CEA were determined in each sample. MonoTotal was determined using an immunoradiometric kit MonoTotal IRMA (IDL Biotech, Sweden), CYFRA 21-1 using immunoradiometric CYFRA 21-1 IRMA kit (Cisbio Bioassays, France) and CEA was determined using chemiluminescent kit and the measurement was performed using the Architect i1000 instrument (Abbott Laboratories, USA) . Statistical software (StatSoft, Inc., USA) was used for all statistical calculations.

Results:
For liver metastases, we found significantly higher levels of all studied markers than for the primary lung tumor and non-tumor diagnoses (both p-value <0.0001). ROC curves show that the ability of assessed markers to distinguish between the tumor group (C34 + C787) and the control is not too strong. Calculated AUC values confirm this fact: MonoTotal=0.6924, CYFRA 21-1=0.6398 and CEA=0.5955. When evaluating the cancer groups separately according to the diagnose ROC curves clearly show that the ability to distinguish hepatic metastases from control group using the evaluated markers is significantly higher than the distinguishing of pulmonary tumor. AUC calculated for liver metastases are: MonoTotal=0.9497, CYFRA 21-1=0.8758 and CEA=0.7514.

Conclusion:
For liver metastases are the levels of all monitored markers significantly higher than in the patients with the primary lung tumors and in the patients with non-tumor diagnoses. ROC curve and AUC clearly show that cytokeratin markers MonoTotal and CYFRA 21-1are highly sensitive markers of liver metastases. CEA, which was used as a marker of metastatic process in the past, did not match so good results as both cytokeratins did. Cytokeratin markers allow for earlier detection of liver metastases and the use of modern oncology and surgical treatments allow prolonged survival and improved quality of life of patients.

Keywords:
Cytokeratin tumor markers, MonoTotal, CYFRA 21-1, CEA, lung carcinoma, liver metastasis.


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