Cytokeratins as serum markers in lung cancer: a comparison of CYFRA 21-1 and TPS.
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.
Pujol
J L
JL
Department of Chest Diseases, Hôpital Arnaud de Villeneuve, Montpellier, France.
Grenier
J
J
Parrat
E
E
Lehmann
M
M
Lafontaine
T
T
Quantin
X
X
Michel
F B
FB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000097:blood* / Q000473:pathology; D005260:Female; D006801:Humans; D007633:Keratins / Q000097:blood*; D008171:Lung Diseases / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D019396:Tissue Polypeptide Antigen
D014408:Biomarkers, Tumor; D010455:Peptides; D019396:Tissue Polypeptide Antigen; D007633:Keratins