Evaluation of tissue polypeptide specific antigen, CYFRA 21-1, and carcinoembryonic antigen in nonsmall cell lung carcinoma: does the combined use of cytokeratin markers give any additional information?

Cancer. 1998 May 15;82(10):1850-9. doi: 10.1002/(sici)1097-0142(19980515)82:10<1850::aid-cncr6>3.0.co;2-r.


Background: Recently developed tissue polypeptide specific antigen (TPS) and CYFRA 21-1 assays determine the soluble cytokeratin 18 and 19 fragments, respectively, in serum. The authors compared the value of TPS, CYFRA 21-1, and carcinoembryonic antigen (CEA) for the diagnosis, staging, prognosis, and monitoring of patients with nonsmall cell lung carcinoma (NSCLC).

Methods: The study included 85 patients with benign lung diseases and 94 patients with NSCLC. TPS, CYFRA 21-1, and CEA serum levels were measured with commercial kits.

Results: The following were demonstrated: 1) CYFRA 21-1 and TPS levels, but not CEA levels, differed significantly between NSCLC patients with operable disease (Stages I-IIIA) and those with inoperable disease (Stages IIIB-IV). 2) The correlation coefficient between CYFRA 21-1 and TPS increased with the progression of NSCLC from Stages I-IIIA (r = 0.41, P = 0.04) to Stages IIIB-IV (r = 0.70, P < 0.001). 3) Multivariate analysis identified TPS and CYFRA 21-1 as significant predictors of survival, with relative risks of 2.57 (P = 0.001) and 2.05 (P = 0.01), respectively. For cases in which both cytokeratin markers were positive, the relative risk was 6.4 (P < 0.0001) compared with cases in which both were negative. 4) For the group with inoperable disease, the combined use of TPS and CYFRA 21-1 allowed for the definition of 3 sets of patients with significantly different median survival times (14.3 months vs. 7.4 months vs. 2.6 months). 5) The percentages of marker evaluations concordant with results of clinical assessments of response to therapy were 75.0%, 72.2%, and 61.1% for CYFRA 21-1, TPS, and CEA, respectively.

Conclusions: These findings suggest that, for NSCLC patients, CYFRA 21-1 and TPS are significant prognostic factors and effective monitors of therapy. The combined use of these cytokeratin markers may provide additional information for prognosis.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / analysis*
  • Biomarkers, Tumor*
  • Carcinoembryonic Antigen / analysis
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Evaluation Studies as Topic
  • Female
  • Humans
  • Keratin-19
  • Keratins / analysis*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Neoplasm Staging
  • Peptides / analysis
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Keratin-19
  • Peptides
  • antigen CYFRA21.1
  • tissue polypeptide specific antigen
  • Keratins