Diagnostic Utility of Serum and Pleural Fluid Carcinoembryonic Antigen, Neuron-Specific Enolase, and Cytokeratin 19 Fragments in Patients With Effusions From Primary Lung Cancer

doi:10.1378/chest.128.4.2298

Chest

Volume 128, Issue 4, October 2005, Pages 2298-2303

https://doi.org/10.1378/chest.128.4.2298 Get rights and content

Study objectives

To assess the diagnostic values of carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragments (CYFRA 21–1) as markers of pleurisy in primary lung cancer.

Design

Prospective case-control study.

Setting

A tertiary university hospital.

Patients

Thirty-four patients with lung cancer and 16 patients with tuberculous pleurisy.

Measurements and results

Levels of CEA, NSE, and CYFRA 21–1 were measured by immunoassay in the serum and pleural fluid of patients with lung cancer and of patients with tuberculous pleurisy. Patients with lung cancer were found to have significantly higher serum and pleural fluid levels of CEA and CYFRA 21–1 than patients with tuberculous pleurisy. Using cutoff values of 5 ng/mL, 20 ng/mL, and 3.3 ng/mL for serum CEA, NSE, and CYFRA 21–1, respectively, the sensitivities and specificities of these tumor markers were as follows for differentiating malignant effusion from benign: CEA, 68% and 93%; NSE, 34% and 93%; and CYFRA 21–1, 45% and 100%. Using cutoff values of 5 ng/mL, 20 ng/mL, and 45 ng/mL for pleural fluid, the sensitivities and specificities were as follows: CEA, 82% and 94%; NSE, 36% and 94%; and CYFRA 21–1, 61% and 81%. A combination of pleural fluid CEA and NSE increased sensitivity and specificity.

Conclusions

In the diagnosis of malignant effusion associated with lung cancer, the determinations of CEA and NSE in pleural fluid could enhance diagnostic yield better than those of all three tumor markers.

Section snippets

Patients

We collected serum and pleural fluid samples from 50 patients admitted to the hospital due to pleural effusion. Effusions were considered malignant if malignant cells were found on cytologic examination or in a biopsy specimen. Only specimens histologically diagnosed as primary malignancies of lung were considered. Malignancies due to any other causes were excluded. Tuberculous pleurisy was diagnosed if one of the following criteria was met: identification of acid-fast bacillus in pleural

Methods

Prior to any therapy, blood and pleural fluid were collected from each patient on the same day. Serum and pleural fluid supernatant were obtained by centrifugation at 1,800 g for 10 min and stored at − 80°C until tumor markers were assayed using commercial immunoassay kits. In both pleural fluid and serum, tumor markers were determined blind of information concerning the definitive diagnosis. CEA, NSE, and CYFRA 21–1 levels were measured using a CEA radioimmunoassay kit (DiaSorin; Stillwater,

Statistical Analysis

All data are expressed as means and SDs or as frequencies. Statistical analysis was performed using statistical software nonparametrically (SPSS-PC; SPSS; Chicago, IL). Differences between the two groups were evaluated using the Mann-Whitney U test, whereas the Kruskal-Wallis test was used to compare three groups. In order to compare the performance of the tumor markers, receiver operating characteristic (ROC) curves were constructed and compared with area under the curve (AUC). The threshold

Results

A total of 16 effusions were defined as benign effusions of tuberculous pleurisy, and 34 were defined as malignant effusion associated with primary lung cancer. There were 21 adenocarcinomas, 5 squamous cell carcinomas, and 8 SCLCs. Of the 16 patients with benign effusion, 8 were men (mean age, 50 years). Of the 34 patients with malignant effusion, 21 were men (mean age, 60 years). All effusions were exudates.

The serum and pleural fluid levels of CEA, NSE, and CYFRA 21–1 in patients with benign

Discussion

In cases of malignant effusion, the cytologic examination is important because of its noninvasiveness and ease. However, we sometimes encounter highly suspected cases of malignant effusion with repeated negative cytology findings. A pleural needle biopsy adds little to cytology, and thus an aggressive diagnostic technique such as thoracoscopy or thoracotomy should be considered.²³ The evaluation of tumor markers in serum and pleural fluid has been proposed as an alternative way of establishing

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Surface-enhanced Raman spectroscopy (SERS) technology has been increasingly integrated with lateral flow immunoassay (SERS-LFA) to enable sensitive and quantitative detection, but SERS-LFA still faces notable challenges. One of the biggest problems is signal variations caused by random distributions of plasmonic SERS immunoprobes. Herein, we develop a sensitive, accurate quantification platform that overcomes this problem with a plasmonic internal standard (PIS), referred to as PIS-LFA. The PIS is achieved by decorating nitrocellulose membranes with Raman reporter molecule-embedded silver-gold alloy nanoparticles. By simultaneously measuring signals of plasmonic immunoprobes and IS and calculating their intensity ratios for signal normalization, we can mitigate signal variations and improve assay sensitivity. Comparing with SERS-LFA in carcinoembryonic antigen (CEA) detection, we show that PIS-LFA achieves a 1.8-fold higher uniformity and 3.2-fold lower limit of detection. We further demonstrate that PIS-LFA exhibits accurate quantification capability in duplex detection of CEA and neuron-specific enolase (NSE) in human sera by performing spike-recovery experiments and validating with electrochemiluminescence immunoassays. As a proof-of-concept, PIS-LFA differentiates levels of serum CEA and NSE between 12 early-stage lung cancer patients and 12 healthy individuals. We believe that PIS-LFA will open up avenues for affordable, rapid, and non-invasive disease screening in point-of-care settings.
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Chest

Clinical InvestigationsDiagnostic Utility of Serum and Pleural Fluid Carcinoembryonic Antigen, Neuron-Specific Enolase, and Cytokeratin 19 Fragments in Patients With Effusions From Primary Lung Cancer

Study objectives

Design

Setting

Patients

Measurements and results

Conclusions

Section snippets

Patients

Methods

Statistical Analysis

Results

Discussion

Chest

Am J Surg

Mayo Clin Proc

Respir Med

Clin Chim Acta

Lung Cancer

Lung Cancer

Lung Cancer

Chest

Chest

Respir Med

Eur J Cancer

Eur J Cancer

Diagnostic efficacy of pleural biopsy as compared with that of pleural fluid examination

Mod Pathol

Pleural effusions related to metastatic malignancies

Clinical Investigations
Diagnostic Utility of Serum and Pleural Fluid Carcinoembryonic Antigen, Neuron-Specific Enolase, and Cytokeratin 19 Fragments in Patients With Effusions From Primary Lung Cancer