Am. J. Respir. Crit. Care Med., Vol 154, No. 3, 09 1996, 725-733.
Cytokeratins as serum markers in lung cancer: a comparison of CYFRA 21- 1 and TPS
JL Pujol, J Grenier, E Parrat, M Lehmann, T Lafontaine, X Quantin and FB Michel
Department of Chest Diseases, Hopital Arnaud de Villeneuve, Montpellier, France.
We examined two recently described cytokeratin markers, CYFRA 21-1
(cytokeratin fragment recognized by KS 19-1 and BM 19-21 antibodies) and
TPS (specific M3 epitope of the tissue polypeptide antigen), in 405 lung
cancer patients (91 small-cell and 314 non-small-cell lung cancers) and 59
patients presenting with nonmalignant pulmonary disease.
Sensitivity-specificity relationship, as analyzed by receiver operating
characteristic curves, demonstrated a higher accuracy of CYFRA 21-1 in
comparison with TPS in both small-cell and non-small-cell lung cancers.
Thresholds of 3.6 ng/ml and 140 U/L for CYFRA 21-1 and TPS respectively
gave a 90% to 95% specificity. Sensitivity of CYFRA 21- 1 was the highest
in squamous-cell carcinomas (0.61) and the lowest in small-cell lung
cancers (0.36), whereas sensitivity of TPS did not vary significantly
according to histology (overall sensitivity, 0.40). In non-small-cell lung
cancers, both serum CYFRA 21-1 and serum TPS distributions varied
significantly according to Mountain's stage of the disease, nodal status,
tumor status, and performance status, inasmuch as the worse each
above-mentioned variable became, the higher the median and interquartile
serum marker level was. Neither CYFRA 21-1 nor TPS was able to accurately
discriminate between stage IIIa (marginally resectable) and stage IIIb
(unresectable) non-small-cell lung cancers, however. In both small-cell and
non-small-cell lung cancers, univariate survival analyses demonstrated that
either a CYFRA 21-1 level over 3.6 ng/ml or a TPS level over 140 U/L
significantly indicated a poor survival rate. In the whole population,
taking into account other significant variables, Cox's model analysis
demonstrated that a poor performance index, an advanced stage of the
disease, the presence of metastases, elevated serum lactate dehydrogenase,
and high serum CYFRA 21-1 (odds ratio, 1.74; 95% confidence interval,
[1.33-2.27] were independent prognostic variables. We concluded that CYFRA
21-1 is a significant determinant of survival. Other applications of
cytokeratin markers in lung cancer are still limited.
