Chest
Volume 126, Issue 6, December 2004, Pages 1757-1763
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Clinical Investigations
PLEURA
Use of a Panel of Tumor Markers (Carcinoembryonic Antigen, Cancer Antigen 125, Carbohydrate Antigen 15–3, and Cytokeratin 19 Fragments) in Pleural Fluid for the Differential Diagnosis of Benign and Malignant Effusions

https://doi.org/10.1378/chest.126.6.1757Get rights and content

Study objective:

The diagnostic value of tumor markers in pleural fluid is subject to debate. The aim of this study was to evaluate the diagnostic performance of several tumor markers in common use for detecting malignant pleural disease.

Design:

Blinded comparison of four tumor markers in pleural fluid with a confirmatory diagnosis of malignancy by pleural cytology or thoracoscopic biopsy.

Setting:

Two teaching hospitals in Spain.

Patients and methods:

A total of 416 patients (166 with definite malignant effusions, 77 with probable malignant effusions, and 173 with benign effusions) were enrolled. Among them, there were 42 patients recruited from one of the participant centers with thoracoscopic facilities, who had false-negative fluid cytology findings and malignancy confirmed by medical thoracoscopy. Tumor markers in pleural fluid were determined either by electrochemiluminescence immunoassay (carcinoembryonic antigen [CEA], carbohydrate antigen 15–3 [CA 15–3], cytokeratin 19 fragments [CYFRA 21–1]) or microparticle enzyme immunoassay (cancer antigen 125 [CA 125]) technologies. Cutoff points that yielded 100% specificity (ie, all patients with benign effusions had levels below this cutoff) were selected for each marker.

Results:

Malignant pleural effusions (PEs) had higher levels of pleural fluid markers than did effusions due to benign conditions. At 100% specificity, a pleural CEA > 50 ng/mL, CA 125 > 2,800 U/mL, CA 15–3 > 75 U/mL, and CYFRA 21–1 > 175 ng/mL had 29%, 17%, 30%, and 22% overall sensitivities, respectively. The combination of the four tumor markers reached 54% sensitivity, whereas the combined use of the cytology and the tumor marker panel increased the diagnostic yield of the former by 18% (95% confidence interval, 13 to 23%). More than one third of cytology-negative malignant PEs could be identified by at least one marker of the panel.

Conclusions:

No single pleural fluid marker seems to be accurate enough as to be introduced in the routine workup of PE diagnosis. However, a tumor marker panel may represent a helpful adjunct to cytology in order to rule in malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

Section snippets

Subjects

We studied 374 patients with PEs attending the Arnau de Vilanova University Hospital (Lleida, Spain) from 1996 to 2002, in whom at least one diagnostic thoracentesis with measurement of CEA, CA 125, CA 15–3, or CYFRA 21–1 in pleural fluid was performed. This series was completed by 42 additional patients recruited from the Virgen del Rocío University Hospital (Sevilla, Spain), who had negative pleural fluid cytology findings but confirmation of pleural malignancy by thoracoscopic biopsy. The

Etiology of PEs

Of the 416 patients who entered the study, 166 patients (86 men and 80 women, with a median age of 67 years) had a malignant PE, 77 patients (41 men and 36 women, with a median age of 69 years) had a probable malignant PE, and 173 patients (109 men and 64 women, with a median age of 67 years) had a benign PE. The specific etiologies and the histologic subtypes of tumors are presented in Table 1. Among the former group, there were 118 patients with positive pleural fluid cytology findings, and

Discussion

A large number of studies on the potential diagnostic usefulness of pleural tumor markers have been published, which report either encouraging1119 or disappointing71215 results. The disagreement in results can be attributed to different factors, including the heterogeneity of tumor types, the inappropriate inclusion of paramalignant PEs to calculate test performances, the sometimes underpowered series, or the use of different methodologies and cutoff values in tumor marker assays, among others.

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    This study was sponsored in part by grants from FIS 00/0699, Ministerio de Sanidad y Consumo, Spain, and from Comité Etico de Investigación Clinica, Arnau de Vilanova University Hospital, Lleida, Spain.

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