Comparison of Cytokeratin Fragment 19 (CYFRA 21-1), Tissue Polypeptide Antigen (TPA) and Tissue Polypeptide Specific Antigen (TPS) as Tumour Markers in Lung Cancer

Abstract

Summary:Recently CYFRA 21-1, a new tumour marker measuring a fragment of cytokeratin 19, was introduced (1,2) and proved to be suitable for the follow-up care and monitoring of the therapy of non-small cell lung carcinomas, especially squamous cell carcinomas of the lung (3, 4). Besides CYFRA 21-1, there are two other tumour markers available, called tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS), which also measure different cytokeratins in serum. In a retrospective study we investigated the clinical significance of these 3 cytokeratin markers in lung cancer compared with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). We investigated the sera of 50 healthy persons, 273 patients with various benign diseases and 218 patients with histologically proven lung cancer. In a first step the specificity versus benign diseases of the lung was established for all the markers, and was fixed at 95%. Then the single and combined sensitivities were calculated. CYFRA 21-1 proved to possess the highest sensitivity in lung cancer in general (61%), in non-small cell lung carcinomas (64%), in squamous cell carcinomas (79%), in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas, neuron-specific enolase proved again to be the marker of first choice (55%). Combined determinations proved clearly increased sensitivity only for large cell carcinomas (CYFRA 21-1 + TPA: 77%) and for small cell lung carcinomas (CYFRA 21-1 + NSE: 62%). From our investigations it was evident that TPA detects at least partly the same substance as CYFRA 21-1 (the sensitivities compared with the markers TPS, CEA, SCC and NSE were rather high, but not as high as for CYFRA 21-1), whereas the TPS assay measures a completely different clinical chemical analyte (lowest number of true positive test results over the whole investigation). These findings correspond cleary to the very recent results of the comparison of CYFRA 21-1, TPA and TPS by immunoblotting (5). Introduction_ ,, , ^.r-r-,^ * ~ * Recently a new tumour marker, called CYFRA 21-1, In many industrialized countries, lung cancer is the was described for the detection of cytokeratin 19-inost common cancer in men and is climbing quickly fragments in serum (1, 2). Cytokeratins and other toward the same incidence in women. Clinical chem-intermediate filaments of the cell like vimentin and ical methods for the support of adequate follow up desmin have become well known since the developcare and the control of efficiency of therapy are avail-ment of monoclonal antibodies in histopathology for able only for small cell lung carcinomas, and they the differentiation and classification of physiological consist of the determination of neuron specific enolase and pathological tissues (8, 9). The expression of a (6, 7).single cytokeratin or a combination of certain cyto-

Clinical evaluation of seven tumour markers in lung cancer diagnosis: can any combination improve the results?

“…Patients with squamous cell carcinoma had the highest SCC values, although this difference was not of statistical signifi. When, however, a specificity of 95% was fixed, CYFRA 21-1, TPM and TPA in that order were found to be the most sensitive index in diagnosing hmg cancer, confirming for CYFRA 21-1 the obsrvations made by Stieber et al (1993a) and Ebert et al (1994). All the other markers had sensitivities below 35% and therefore could not be considred singly as useful markers of different types of lung cancer.…”

“…CYFRA 21-1 detects a fragment of cytokeratin 19 (Pujol et al, 1993). Of these markers, TPA and CYFRA 21-1 seem to be the most sensitive and specific serum markers of lung cancer (Mizushima et al, 1991;Stieber et al, 1993a;Ebert et al, 1994).…”

“…Squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) have been extensively studied in patients with lung cancer; however, their sensitivity and specificity have usually been reported as low (Mizushima et al, 1991;Jarvisalo et al, 1993;Ebert et al, 1994). Few reports deal with a combined evaluation of various tumour markers in lung cancer diagnosis (Mizushima et al, 1991;Jarvisalo et al, 1993;Stieber et al, 1993a;Ebert et al, 1994).…”

Serum-based protein biomarkers for detection of lung cancer

“…A specificity of 100% is desirable in clinical terms [59], but may not be always practical as it may become less sensitive. Several researchers therefore use a specificity of 95% as the cut-off point [60]. The connection between sensitivity and specificity for a particular disease under prediction assigns suitable cut-off points, which give rise to a receiver operatingcharacteristic (ROC) curve.…”

Cytokeratin 18 (CK18) and Caspase-Cleaved CK18 (ccCK18) as Response Markers in Anticancer Therapy

“…The three most commonly applied CK markers overall are TPA, TPS and CYFRA 21-1. TPA is a broadspectrum test that measures CKs 8, 18 and 19, while TPS and CYFRA 21-1 measure CKs 18 and 19, respectively (Weber et al, 1984;Stieber et al, 1993;Sundström et al, 1994;Stigbrand et al, 1998;Barak et al, 2004).…”