Immunocytochemistry and ELISA quantitation of mucin for diagnosis of malignant pleural effusions

Our plain-English summary of Immunocytochemistry and ELISA quantitation of mucin for diagnosis of malignant pleural effusions, by P.C. Yang, K.T. Luh, S.H. Kuo, et al (The American Review of Respiratory Disease, 1992).

The study

• Authors: P.C. Yang, K.T. Luh, S.H. Kuo, C.W. Wu
• Journal: The American Review of Respiratory Disease
• Published: 1992;146(6):1571-5
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

One hundred and thirty-five pleural effusions with definite etiology were analyzed by mucin-specific monoclonal antibody (17Q2)-derived enzyme-linked immunosorbent assay (ELISA). Twenty-four effusions were transudate, 45 were nonmalignant exudate, and 66 were malignant. Among the 66 malignant effusions, 52 were adenocarcinoma, and 14 were malignancies other than adenocarcinoma. Purified mucous glycoproteins from sputa of normal subjects were used as ELISA standard. Our results showed that the mean mucin concentration in malignant pleural effusions were significantly higher than that of benign exudates (8.41 +/- 13.48 ng/ml versus 1.09 +/- 0.82 ng/ml, p < 0.01). Mucin concentration in malignant pleural effusions caused by adenocarcinoma was also significantly higher than in non-adenocarcinoma effusions (9.96 +/- 14.81 ng/ml versus 2.66 +/- 1.74 ng/ml, p < 0.01). With the use of mean +/- 2 SD of mucin concentration in benign exudates as a cut-off value (2.73 ng/ml), the sensitivity of this assay for diagnosis of malignant effusions was 66.7%, specificity was 97.1%, and accuracy was 82.2%. High levels of mucin concentration were more specifically associated with adenocarcinoma. When the mucin concentration in pleural effusions was greater than 5 ng/ml, 93.1% (27/29) of patients were adenocarcinoma. If the mucin concentration was greater than 10 ng/ml, 100% (14/14) of patients were adenocarcinoma. Immunofluorescent staining by mucin-specific monoclonal antibody 17Q2 were also carried out in diastase-treated cell preparations obtained from 22 patients with malignant pleural effusions and 16 benign exudates. Nine of 14 adenocarcinomas (64.2%) were reactive with monoclonal antibody 17Q2, while none of the benign exudates, squamous cell carcinomas, and mesotheliomas were stained.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This study tested whether measuring mucin, an airway mucus substance, in fluid around the lungs (pleural effusion) could help diagnose cancer. Using an antibody-based laboratory test (ELISA), the authors analyzed fluid from 135 consecutive patients at National Taiwan University Hospital in 1989. There were 24 transudates, 45 nonmalignant exudates and 66 malignant effusions, 52 of them adenocarcinoma. Mean mucin was 8.41 ng/ml in malignant effusions versus 1.09 ng/ml in benign exudates (p less than 0.01). At a cut-off of 2.73 ng/ml, sensitivity was 66.7% and specificity 97.1%. Both false positives had tuberculous pleurisy. Seventeen of 30 malignant effusions with negative cytology were above the cut-off. All 14 effusions above 10 ng/ml were adenocarcinoma. Antibody staining was tested on cells from 22 malignant effusions already shown malignant by routine cytology, and 16 benign exudates. It stained nine of 14 adenocarcinomas, but no squamous cell carcinomas (six), mesotheliomas (two) or benign exudates. Mucin did not correlate well with survival in 30 malignant-effusion patients who did not receive systemic chemotherapy. Calling the study preliminary, the authors concluded both methods may be potentially useful for diagnosing malignant pleural effusions.

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: Diagnostic test evaluation in consecutive hospital patients, described by the authors as preliminary. Mucin in pleural fluid was measured in the laboratory, and cells from the fluid were immunostained.
• Who was studied: 135 consecutive patients with pleural effusions of definite cause, seen at National Taiwan University Hospital from January to December 1989. They were 86 males and 49 females, aged 16 to 85. There were 24 transudates, 45 nonmalignant exudates and 66 malignant effusions (52 adenocarcinoma, 14 other malignancies). Immunostaining was done on cells from 16 benign exudates and from 22 malignant effusions whose malignant cells had been documented by conventional cytology (14 adenocarcinoma, 6 squamous cell carcinoma, 2 mesothelioma).
• Exposure: No asbestos or other environmental or occupational exposure was studied. The article evaluates a diagnostic test: mucin measured by ELISA, and cell staining with the mucin-specific monoclonal antibody 17Q2.
• Main results:
  • Mean mucin concentration was higher in the 66 malignant effusions than in the 45 benign exudates: 8.41 ± 13.48 ng/ml versus 1.09 ± 0.82 ng/ml, p less than 0.01. The 24 transudates had a mean of 0.64 ± 0.49 ng/ml.
  • Among malignant effusions, mean mucin was higher in adenocarcinoma than in non-adenocarcinoma malignancies: 9.96 ± 14.81 ng/ml versus 2.66 ± 1.74 ng/ml, p less than 0.01.
  • The cut-off was 2.73 ng/ml, the mean plus 2 SD of benign exudates. At that cut-off, sensitivity for malignant effusions was 66.7% (44/66), specificity was 97.1% (67/69 nonmalignant effusions) and accuracy was 82.2%.
  • Both false-positive results were in patients with tuberculous pleurisy.
  • Of 30 malignant effusions with negative cytology, 17 (56.7%) had mucin above 2.73 ng/ml. Of 36 with positive cytology, 27 (75.0%) did.
  • Above 5 ng/ml, 27 of 29 patients (93.1%) had adenocarcinoma. Above 10 ng/ml, 14 of 14 (100%) had adenocarcinoma.
  • The malignant samples chosen for immunostaining all had malignant cells already documented by conventional cytology.
  • In immunostaining, nine of 14 adenocarcinoma samples were positive. None of the 6 squamous cell carcinomas, 2 mesotheliomas or 16 benign exudates stained.
  • In 30 patients with malignant effusions who did not receive systemic chemotherapy, mucin levels did not correlate well with survival time (r = 0.197, p greater than 0.10).
• The authors' conclusion: The authors concluded that, in this preliminary study, ELISA measurement of pleural fluid mucin and immunostaining with the mucin-specific antibody may be potentially helpful in assisting the diagnosis of malignant pleural effusions.
• Limitations the authors state:
  • Only a limited number of specimens were examined by immunostaining, so the authors said further study is needed to confirm the staining findings.
  • High mucin levels were not limited to lung adenocarcinoma. They also occurred with metastatic adenocarcinoma from the breast, stomach and colon, which suggests the antibody may cross-react with mucins from other cancers.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Etiology, Monoclonal Antibody, Exudate, Adenocarcinoma, Glycoprotein, Squamous Cell Carcinoma, Mesothelioma.

Related studies

• Cytological differential diagnosis among adenocarcinoma, epithelial mesothelioma, and reactive mesothelial cells in serous effusions by immunocytochemistry — X.Y. Su, G.D. Li, et al. (2011)
• The application of immunocytochemistry to direct smears in the diagnosis of effusions — S.M. Knoepp, J. Placido, et al. (2013)
• 'Mucin-positive' epithelial mesothelioma of the peritoneum: an unusual diagnostic pitfall — D.S. Cook, R.L. Attanoos, et al. (2000)
• Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions — M. Miédougé, P. Rouzaud, et al. (1999)
• Small orangiophilic squamous-like cells: an underrecognized and useful morphological feature for the diagnosis of malignant mesothelioma in pleural effusion cytology — L. Chen, S.G. Caldero, et al. (2014)
• Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis — T. Sabo-Attwood, M. Ramos-Nino, et al. (2005)

Browse more research in The American Review of Respiratory Disease, or return to medical research.