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

Our plain-English summary of Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions, by M. Miédougé, P. Rouzaud, G. Salama, et al (British Journal of Cancer, 1999).

The study

• Authors: M. Miédougé, P. Rouzaud, G. Salama, M.C. Pujazon, C. Vincent, M.A. Mauduyt, J. Reyre, P. Carles, G. Serre
• Journal: British Journal of Cancer
• Published: 1999;81(6):1059-65
• Cited by: 72 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Carcinoembryonic antigen (CEA), carbohydrate antigens 15-3, 19-9 and 72-4 (CA 15-3, CA 19-9 and CA 72-4), cytokeratin 19 fragments (CYFRA 21-1), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) were evaluated in pleural fluid for the diagnosis of malignant effusions. With a specificity of 99%, determined in a series of 121 benign effusions, the best individual diagnostic sensitivities in the whole series of 215 malignant effusions or in the subgroup of adenocarcinomas were observed with CEA, CA 15-3 and CA 72-4. As expected, a high sensitivity was obtained with SCC in squamous cell carcinomas and with NSE in small-cell lung carcinomas. CYFRA and/or CA 15-3 were frequently increased in mesotheliomas. Discriminant analysis showed that the optimal combination for diagnosis of non-lymphomatous malignant effusions was CEA + CA 15-3 + CYFRA + NSE: sensitivity of 94.4% with an overall specificity of 95%. In malignant effusions with a negative cytology, 83.9% were diagnosed using this association. The association CYFRA + NSE + SCC was able to discriminate adenocarcinomas from small-cell lung cancers. Regarding their sensitivity and their complementarity, CEA, CA 15-3, CYFRA 21-1, NSE and SCC appear to be very useful to improve the diagnosis of malignant pleural effusions.

In plain English

This retrospective study, from Purpan Hospital in Toulouse, France, measured seven tumour markers (CEA, CA 15-3, CA 19-9, CA 72-4, CYFRA 21-1, NSE and SCC) in fluid collected around the lungs (pleural effusions) of patients. There were 336 effusions: 121 from patients with benign disease and 215 from patients with cancer, including 11 with mesothelioma. Asbestos exposure was not studied. Cut-off levels were set so that 99% of benign effusions tested negative (97.5% for NSE). A combination of four markers (CEA, CA 15-3, CYFRA and NSE) detected 94.4% of non-lymphoma cancer effusions, with an overall specificity of 95%. It also detected 26 of 31 (83.9%) non-lymphoma cancers whose fluid showed no cancer cells on cytology. In the 11 mesotheliomas, CYFRA was raised in 54.5%, CA 15-3 in 45.5% and CEA in 0.0%. The four-marker combination detected 72.7% of them. The markers did not reliably separate mesothelioma from adenocarcinoma: only 2 of 11 mesotheliomas were classified correctly. The authors concluded that the four-marker combination showed high sensitivity and a broad spectrum for diagnosing malignancy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective diagnostic study of tumour markers measured in stored pleural fluid samples
• Who was studied: 336 pleural effusions from patients of the Department of Internal Medicine, Purpan Hospital, Toulouse, France. 121 were benign (including 3 labelled benign asbestosis) and 215 were malignant (including 11 mesotheliomas). The series was 156 effusions from a previous report plus 180 obtained from July 1996 to December 1997.
• Exposure: Not an exposure study; no asbestos or occupational exposure was assessed. What was studied was the level of seven tumour markers (CEA, CA 15-3, CA 19-9, CA 72-4, CYFRA 21-1, NSE, SCC) in pleural fluid.
• Main results:
  • At cut-offs giving 99% specificity, sensitivity across all 215 malignant effusions was 60.0% for CEA, 63.7% for CA 15-3, 42.8% for CYFRA, 20.9% for CA 19-9 and 68.4% for CA 72-4.
  • SCC levels did not differ significantly between benign (median 1.6 ng/ml) and malignant (median 2.2 ng/ml) effusions (P = 0.22). All other markers were significantly higher in malignant effusions.
  • In the 11 mesotheliomas, individual marker sensitivity was 0.0% for CEA, 45.5% for CA 15-3 and 54.5% for CYFRA.
  • The combination CEA + CA 15-3 + CYFRA + NSE had a sensitivity of 88.4% for all malignant effusions and 94.4% for non-lymphomatous malignant effusions, with an overall specificity of 95%.
  • In non-lymphomatous malignant effusions with negative cytology, the four-marker combination detected 26 of 31 (83.9%).
  • For mesotheliomas, the four-marker combination detected 72.7% of all 11, and 71.4% of the 7 with negative cytology.
  • When the markers were used to predict tumour type, 9 of 11 mesotheliomas were predicted as adenocarcinomas and 2 were correctly classified (18.2%).
  • Only 64.8% of adenocarcinomas with a known primary site were correctly classified by organ of origin.
• The authors' conclusion: The authors concluded that, in a large series of pleural effusions, the combination of CEA, CA 15-3, CYFRA and NSE showed high sensitivity and a broad spectrum for diagnosing malignancy.
• Limitations the authors state:
  • In small-cell and squamous cell lung carcinomas, too few patients had cytologically negative effusions to evaluate the markers in that situation.
  • The panel, based on epithelial markers, was inadequate for diagnosing lymphomas.
  • The authors stated that a multicentre, prospective study with this panel would be needed to establish the markers' place in managing pleural effusions.

Topics

Medical terms in this study, explained in our Lexicon: Carcinoembryonic Antigen (CEA), Squamous Cell Carcinoma, Adenocarcinoma, Carcinoma, Mesothelioma, Cytology, Lung Cancer, Pleural Effusion.

Related studies

• Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions — G. Salama, M. Miédougé, et al. (1998)
• EZH2, a unique marker of malignancy in effusion cytology — H. Jiang, R. Gupta, et al. (2014)
• Detection of cancer cells in effusions from patients diagnosed with gynaecological malignancies. Evaluation of five epithelial markers — B. Davidson, B. Risberg, et al. (1999)
• Diagnostic usefulness of tumour marker levels in pleural effusions of malignant and benign origin — F. Kuralay, Z. Tokgöz, et al. (2000)
• Use of cholesterol and soluble tumour markers CEA and syndecan-2 in pleural effusions in cases of inconclusive cytology — M. Gulyas, J. Fillinger, et al. (2019)
• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)

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