Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer
The serum tumor markers CYFRA 21–1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21–1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS.
KeywordsSerum CYFRA 21–1 Cytologic tumor marker Cytologic SCC Ag Prognosis NSCLC
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology (2010-0009053).
Conflicts of interest
- 5.Tanaka K, Hata A, Kaji R, Fujita S, Otoshi T, Fujimoto D, et al. Cytokeratin 19 fragment predicts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor in non-small-cell lung cancer harboring EGFR mutation. J Thorac Oncol. 2013;8(7):892–8. doi: 10.1097/JTO.0b013e31828c3929.CrossRefPubMedGoogle Scholar
- 6.Nisman B, Biran H, Heching N, Barak V, Ramu N, Nemirovsky I, et al. Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer: association of marker changes after two chemotherapy cycles with different measures of clinical response and survival. Br J Cancer. 2008;98(1):77–9. doi: 10.1038/sj.bjc.6604157.CrossRefPubMedGoogle Scholar
- 8.Molina R, Filella X, Auge JM, Fuentes R, Bover I, Rifa J, et al. Tumor markers (CEA, CA 125, CYFRA 21–1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors. Tumour Biol. 2003;24(4):209–18.CrossRefPubMedGoogle Scholar
- 11.Kim GR, Hur J, Lee HJ, Nam JE, Kim YJ, Hong YJ, et al. Analysis of tumor markers in cytological fluid obtained from computed tomography-guided needle aspiration biopsies for the diagnosis of ground-glass opacity pulmonary lesions. Cancer Cytopathology. 2013;121(4):214–22. doi: 10.1002/cncy.21244.CrossRefPubMedGoogle Scholar
- 14.Hur J, Lee HJ, Byun MK, Nam JE, Moon JW, Kim HS, et al. Computed tomographic fluoroscopy-guided needle aspiration biopsy as a second biopsy technique after indeterminate transbronchial biopsy results for pulmonary lesions: comparison with second transbronchial biopsy. J Comput Assist Tomogr. 2010;34(2):290–5. doi: 10.1097/RCT.0b013e3181bc93ef.CrossRefPubMedGoogle Scholar
- 15.Hong YJ, Hur J, Lee HJ, Nam JE, Kim YJ, Kim HS, et al. Analysis of tumor markers in the cytological fluid obtained from computed tomography-guided needle aspiration biopsy for the diagnosis of non-small cell lung cancer. J Thorac Oncol. 2011;6(8):1330–5. doi: 10.1097/JTO.0b013e31822462b1.CrossRefPubMedGoogle Scholar
- 21.Ardizzoni A, Cafferata MA, Tiseo M, Filiberti R, Marroni P, Grossi F, et al. Decline in serum carcinoembryonic antigen and cytokeratin 19 fragment during chemotherapy predicts objective response and survival in patients with advanced nonsmall cell lung cancer. Cancer. 2006;107(12):2842–9. doi: 10.1002/cncr.22330.CrossRefPubMedGoogle Scholar
- 24.Picardo AL, Diez M, Torres A, Maestro M, Ortega D, Hernando F, et al. Analysis of the prognostic significance of cytosolic determination of CA 125 tumor-associated antigen, carcinoembryonic antigen and squamous cell carcinoma antigen in patients with nonsmall cell lung carcinoma. Cancer. 1996;77(6):1066–72.Google Scholar