Cytokeratins as serum markers in lung cancer: a comparison of CYFRA 21-1 and TPS.

Abstract

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.

The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease

“…However, in our study, the prognostic value of Cyfra 21-1 is independent of the stage of the disease. Our findings are in agreement with those of Pujol et al (Pujol et al, 1993(Pujol et al, , 1996, who report that the prognostic significance obtained by Cyfra 21-1 in squamous cell lung cancer is independent and adds to the information obtained from other classic prognostic factors, such as extent of the disease, weight loss, performance status, etc. Niklinski and colleagues report that Cyfra 21-1 may be an independent prognostic parameter of survival and tumour relapse in squamous cell lung cancer (Niklinski et al, 1996).…”

CYFRA 21-1 is a prognostic determinant in non-small-cell lung cancer: results of a meta-analysis in 2063 patients

“…By analysing the different prognostic studies (Ebert et al, 1993(Ebert et al, , 1997Pujol et al, 1993aPujol et al, , 1996Pujol et al, , 2001aGiovanella et al, 1995;Moro et al, 1995;Paesmans et al, 1995a;Wieskopf et al, 1995;Szturmowicz et al, 1996;Brechot et al, 1997;Hamzaoui et al, 1997;Takei et al, 1997;Hirashima et al, 1998;Niklinski et al, 1998;Nisman et al, 1998Nisman et al, , 1999Foa et al, 1999;Kashiwabara et al, 2000;Buccheri et al, 2003), one can observe that there are some uncertainties regarding the exact hazard ratio of risk of death associated with a high serum CYFRA 21-1 level insofar as the estimated values range from 1.05 (Moro et al, 1995) to 2.8 (Wieskopf et al, 1995). This discrepancy is puzzling and might reflect both the relatively small size of the studies and the inconstancy of co-variables introduced in the proportional hazards model.…”

Cytokeratin 8: The Dominant Type II Intermediate Filament Protein in Lung Cancer

“…The values of both Cyfra 21-1 and TPS significantly reflected the disease stage in NSCLC. However, when multivariate analysis was performed to take into account other significant factors, only Cyfra 21-1, and not TPS, was confirmed to be an independent prognostic factor (Pujol et al, 1996).…”

“…Studies of patients with lung diseases of either neoplastic or non-neoplastic origin revealed TPS sensitivity rates between 13-54% (Correale et al, 1994;Giovanella et al, 1995;Nisman et al, 1998;Pujol et al, 1994;Pujol et al, 1996;van der Gaast et al, 1994). TPS sensitivity did not vary in NSCLC with different histology, but it did differ according to the progression of lung cancer (Giovanella et al, 1995;Pujol et al, 1996).…”

“…Pendleton et al analyzed serum samples from 24 patients with NSCLC, and detected full length protein of both CK8 and CK18 (Pendleton et al, 1994). In contrast, type I CKs are easily digested by caspases during apoptosis, and these fragments are indeed detected in the circulation as Cyfra 21-1 and as caspase-cleaved CK18 (Buccheri & Ferrigno, 2001;Kramer et al, 2004;Linder et al, 2010;Pujol et al, 1993;Pujol et al, 1996). Unlike type I CKs, type II CKs do not appear to be good caspase substrates.…”