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 (cy tokeratin fragment recognized by KS 19-1 and BM 19-21 antibodies) and TPS (specific M3 epitope of the tissue polypeptide antigen), in 405 lu ng cancer patients (91 small-cell and 314 non-small-cell lung cancers) and 59 patients presenting with nonmalignant pulmonary disease. Sensi tivity-specificity relationship, as analyzed by receiver operating cha racteristic curves, demonstrated a higher accuracy of CYFRA 21-1 in co mparison 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 respectivel y gave a 90% to 95% specificity. Sensitivity of CYFRA 21-1 was the hig hest in squamous-cell carcinomas (0.61) and the lowest in small-cell l ung cancers (0.36), whereas sensitivity of TPS did not vary significan tly according to histology (overall sensitivity, 0.40). In nonsmall-ce ll lung cancers, both serum CYFRA 21-1 and serum TPS distributions var ied significantly according to Mountain's stage of the disease, nodal status, tumor status, and performance status, inasmuch as the worse ea ch above-mentioned variable became, the higher the median and interqua rtile serum marker level was. Neither CYFRA 21-1 nor TPS was able to a ccurately discriminate between stage IIIa (marginally resectable) and stage IIIb (unresectable) non-small-cell lung cancers, however. In bot h small-cell and non-small-cell lung cancers, univariate survival anal yses demonstrated that either a CYFRA 21-1 level over 3.6 ng/ml or a T PS 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 se rum lactate dehydrogenase, and high serum CYFRA 21-1 (odds ratio, 1.74 ; 95% confidence interval, [1.33-2.27]) were independent prognostic va riables. We concluded that CYFRA 21-1 is a significant determinant of survival. Other applications of cytokeratin markers in lung cancer are still limited.