CEA, CA 15-3 and CYFRA 21-1 in serum and pleural fluid of patients with pleural effusions

Abstract

The role of tumour marker assays in differentiating malignant from benign pleural effusions is not yet clear. This study was designed to prospectively assess the individual and combined diagnostic utility of three tumour markers in patients with pleural effusion.Pleural and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3) and cytokeratin 19 fragment (CYFRA 21-1) were determined in 115 patients with pleural effusions (42 malignant and 73 benign). The diagnostic utility of each tumour marker was assessed using accuracy to determine the optimal cut-off point, whilst a logistic regression model was used to obtain the optimal combined test.In serum, every marker showed an individual high specificity (over 97%) for malignancy. The sensitivity of CEA, CA 15-3 and CYFRA 21-1 was 36, 48 and 31%, respectively. In patients without renal failure, the sensitivity of CYFRA 21-1 rose to 53%, while those of CEA and CA 15-3 remained almost unchanged. In pleural fluid, CYFRA 21-1 showed low sensitivity (32%) and specificity (82%), while CEA showed the highest sensitivity (57%). Excluding patients with renal failure, the combined determination in serum of CEA, CA 15-3 and CYFRA 21-1 has a high accuracy (88%), similar to that for CEA plus CA 15-3 in pleural fluid (87%).We conclude that CYFRA 21-1 is useless in pleural fluid and should not be used in serum for patients with renal failure. The combined determination of CEA, CA 15-3 and CYFRA 21-1 in serum may obviate its determination in pleural fluid.

Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions

“…Furthermore, compared to CEA and CA 72-4, CA 15-3 showed an atypical pattern in mesotheliomas, with a sensitivity of 45.5%, in agreement with the results of Villena et al (1996). The data published for pleural CYFRA are more controversial, notably concerning the thresholds and the overall sensitivity which is described as either higher (Satoh et al, 1995) or lower than the sensitivity of CEA (Romero et al, 1996). Confirming our prior study (Salama et al, 1998), we observed similar sensitivities for pleural CEA and pleural CYFRA but above all, a high sensitivity for pleural CYFRA in mesotheliomas.…”

“…Few studies on pleural fluid have integrated CA 72-4 (Ferroni et al, 1990, Villena et al, 1996 and our results confirmed the high sensitivity of CA 72-4 in all types of adenocarcinomas, but we also noted high levels in squamous cell carcinomas. Similarly, as previously described (Ferroni et al, 1990, Romero et al, 1996Villena et al, 1996), we observed high values of CA 15-3 in adenocarcinomas and not only in those of breast origin. Furthermore, compared to CEA and CA 72-4, CA 15-3 showed an atypical pattern in mesotheliomas, with a sensitivity of 45.5%, in agreement with the results of Villena et al (1996).…”

“…the use of serum thresholds, being chosen in numerous cases. Indeed, at the same level of specificity, pleural and serum thresholds are different, as shown for CEA (Rittgers et al, 1978, Romero et al, 1996 and also for CYFRA (Toumbis et al, 1996). In patients with malignant effusions, pleural values of markers are higher than serum values and the greater sensitivity of the pleural assay for the diagnosis of malignancy was demonstrated for several markers such as CEA (Rittgers et al, 1978;Klockars et al, 1980;Asseo and Tracopoulos, 1982;Rapellino et al, 1990;Romero et al, 1996), CA 15-3 (Rapellino et al, 1990) or neuron-specific enolase (NSE) (Menard et al, 1993).…”

Methods and biomarkers for the diagnosis and prognosis of cancer and other diseases: Towards personalized medicine

“…Upon induction of apoptosis, their proteolytic fragments are released from dying cells and can serve as cell-death markers in vivo. In particular, two markers have been frequently used in the clinic for over 10 years: a caspase-generated, 13 kDa proteolytic fragment of human cytokeratin-18, also known as "serum tissue polypeptide-specific antigen" (TPS), and a ∼30 kDa fragment of cytokeratin-19, also called "watersoluble cytokeratin-19 fragment" or CYFRA 21-1 (Romero et al, 1996). Both markers have been traditionally considered as biochemical indicators of tumor burden and cell death within the epithelium, since they do not discriminate between normal and malignant cells.…”

Avaliação citogenética molecular de células do líquido pleural de pacientes com derrame pleural maligno

“…Segundo dados de literatura, a sensibilidade do exame citológico no diagnóstico de derrame pleural maligno é, em geral, inferior a 60% 14,61 . Shidhan e …”