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


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

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.

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.

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.

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


1. Liška, V., Třeška, V., Holubec, L., Skalický, T., Sunar, A., Topolčan, O., Fínek, J. Prognostické faktory časné recidivy metastatického procesu jater u kolorektálního karcinomu a jejich použití v klinické praxi. Rozhl Chir, 2006, 85, p. 163-168.

2. Barak, V., Goike, H., Panaretakis, K. W., Einarsson, R. Clinical utility of cytokeratins as tumor markers. Clin Biochem, 2004, 37, 529-40.

3. Brattström, D., Wagenius, G., Sandström, P., Dreilich, M., Bergström, S., Goike, H., Hesselius, P., Bergqvist, M. Newly developed assay measuring cytokeratins 8, 18 and 19 in serum is correlated to survival and tumor volume in patients with esophageal carcinoma. Dis Esophagus, 2005, 18, p. 298-303.

4. Giovanella, L., Treglia, G., Verburg, F. A., Salvatori, M., Ceriani, L. Serum cytokeratin 19fragments: a dedifferentiation marker in advanced thyroid cancer. Eur J Endocrinol, 2012, 167, p. 793-7.

5. Fernandez-Cotarelo, M. J., Guerra-Vales, J. M., Colina, F., de la Cruz, J. Prognostic factors in cancer of unknown primary site. Tumori, 2010, 96, p. 111-6.

6. López-Gómez, M., Cejas, P., Merino, M., Fernández-Luengas, D., Casado, E., Feliu, J. Management of colorectal cancer patients after resection of liver metastases: can we offer a tailored treatment? Clin Transl Oncol, 2012, 14, p. 641-58.

7. Třeška, V., Vodička, J., Špidlen, V., Skalický, T., Fichtl, J., Šimánek, V., Šafránek, J., Sutnar, A., Brůha, J. Jaterní a plicní metastázy kolorektálního karcinomu – zkušenosti Chirurgické kliniky FN v Plzni. Rozhl Chir, 2013, 92, p. 488-93.

8. Sakamoto, Y,. Miyamoto, Y., Beppu, T., Nitta, H., Imai, K., Hayashi, H., Baba, Y., Yoshida, N., Chikamoto, A., Baba, H. Post-chemotherapeutic CEA and CA19-9 Are Prognostic Factors in Patients with Colorectal Liver Metastases Treated with Hepatic Resection After Oxaliplatin-based Chemotherapy. Anticancer Res, 2015, 35, p. 2359-68.

9. Hinz, S., Tepel, J., Röder, C., Kalthoff, H., Becker, T. Profile of serum factors and disseminated tumor cells before and after radiofrequency ablation compared to resection of colorectal liver metastases-a pilot study. Anticancer Res, 2015, 35, p. 2961-7.

10. Holdenrieder, S., Stieber, P., Liska, V., Treska, V., Topolcan, O., Dreslerova, J., Matejka, V. M., Finek, J., Holubec, L. Cytokeratin serum biomarkers in patients with colorectal cancer. Anticancer Res, 2012, 32, p. 1971-6.

11. Eriksson, P., Brattström, D., Hesselius, P., Larsson, A., Bergström, S., Ekman, S., Goike, H., Wagenius, G., Brodin, O., Bergqvist, M. Role of circulating cytokeratin fragments and angiogenic factors in NSCLC patients stage IIIa-IIIb receiving curatively intended treatment. Neoplasma, 2006, 53, p. 285-90.

12. Buccheri, G., Ferrigno, D. Lung tumor markers of cytokeratin origin: an overview. Lung Cancer, 2001, 34, p. 65-9.

13. Haas, M., Kern, C., Kruger, S., Michl, M., Modest, D. P., Giessen, C., Schulz, C., von Einem, J. C., Ormanns, S., Laubender, R. P., Holdenrieder, S., Heinemann, V., Boeck, S. Assessing novel prognostic serum biomarkers in advanced pancreatic cancer: the role of CYFRA 21-1, serum amyloid A, haptoglobin, and 25-OH vitamin D3. Tumour Biol, 2015, 36, p. 2631-40.

14. Goldstein, M. J., Mitchell, E. P. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer Invest, 2005, 23, p. 338-51.

15. Sakamoto, Y., Miyamoto, Y., Beppu, T., Nitta, H., Imai, K., Hayashi, H., Baba, Y., Yoshida, N., Chikamoto, A., Baba, H. Post-chemotherapeutic CEA and CA19-9 Are Prognostic Factors in Patients with Colorectal Liver Metastases Treated with Hepatic Resection After Oxaliplatin-based Chemotherapy. Anticancer Res, 2015, 35, p. 2359-68.

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