Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology

Our plain-English summary of Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology, by T. Oda, S. Ogata, S. Kawaguchi, et al (Diagnostic Cytopathology, 2016).

The study

• Authors: T. Oda, S. Ogata, S. Kawaguchi, S. Minabe, M. Dokyu, H. Takahashi, F. Kumazawa, H. Shimazaki, M. Takano, K. Hase, Y. Ozeki, S. Kanoh, K. Nakanishi
• Journal: Diagnostic Cytopathology
• Published: 2016;44(6):499-504
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Recently, claudin-4 (CL4) immunocytochemistry was reported to be useful for differential diagnosis in effusion cytology. We wondered whether CL4 might be useful for "single-shot" identification of metastatic carcinoma. The purpose of this study was to evaluate the usefulness of CL4 in effusion cytology.

Methods: In total, 266 cases (169 metastatic carcinomas, eight malignant mesotheliomas, and 89 reactive mesothelial cells) were selected. Immunocytochemical examinations of cell-block sections were performed for CL4, Ber-EP4, and MOC-31. We used an arbitrary 4-tiered scale based on both staining intensity and positive-cell percentage among all target cells, and calculated a staining index score (sum of the above two scores).

Results: In a ROC-curve analysis, higher area-under-curve values were found for CL4 than for Ber-EP4 or MOC-31 (0.982, 0.942, and 0.926, respectively).

Conclusions: Since CL4 exhibited similar or superior usefulness to Ber-EP4 and MOC-31, it could become the first choice for the above differential diagnosis in effusion cytology. Diagn. Cytopathol. 2016;44:499-504. © 2016 Wiley Periodicals, Inc.

© 2016 Wiley Periodicals, Inc.

In plain English

This laboratory study from the National Defense Medical College Hospital in Tokorozawa, Japan, tested whether a stain for the protein claudin-4 helps tell metastatic carcinoma (cancer that has spread from elsewhere) apart from malignant mesothelioma and from benign reactive mesothelial cells in body-fluid samples (effusions). It did not study asbestos exposure. The authors used 266 fluid samples collected between July 2008 and November 2014: 169 metastatic carcinomas, 8 malignant mesotheliomas and 89 reactive mesothelial cell cases. Each sample was stained for claudin-4 and for two established markers, Ber-EP4 and MOC-31, and scored on a combined intensity-and-percentage scale. Claudin-4 scored highest on an overall accuracy measure (area under the curve 0.982, versus 0.942 for Ber-EP4 and 0.926 for MOC-31). Claudin-4 identified 96.4% of the carcinomas and was negative in all 97 mesothelioma and reactive samples. The other two markers stained a few of those samples. Claudin-4 detected only 69.2% of the carcinomas that were not adenocarcinomas. The authors concluded that claudin-4 was superior to Ber-EP4 and MOC-31 for this distinction and might be considered the first choice.

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 accuracy study of stored effusion cell-block samples, comparing three antibody stains with ROC-curve analysis
• Who was studied: 266 effusion samples (128 pleural, 135 peritoneal, 3 pericardial) from 266 patients aged 17 to 86 at the National Defense Medical College Hospital, Tokorozawa, Japan, July 2008 to November 2014. The samples were 169 metastatic carcinomas, 8 malignant mesotheliomas and 89 benign (reactive mesothelial cell) effusions. False-positive and false-negative cases and samples too small to evaluate were excluded.
• Exposure: No asbestos or other environmental exposure was studied. The tests compared were immunostains for claudin-4 (CL4), Ber-EP4 and MOC-31 on cell-block sections.
• Main results:
  • For distinguishing metastatic carcinoma from malignant mesothelioma and reactive mesothelial cells, the area-under-curve values were 0.982 for claudin-4, 0.942 for Ber-EP4 and 0.926 for MOC-31.
  • At the best cut-off (staining index score 2), sensitivity and specificity were 96.4% and 100% for claudin-4, 88.8% and 98.0% for Ber-EP4, and 86.4% and 96.9% for MOC-31.
  • For each antibody, positive samples were significantly more common among metastatic carcinomas than among malignant mesotheliomas and reactive mesothelial cells (P less than 0.0001 for each).
  • Claudin-4 was negative in all malignant mesothelioma and reactive mesothelial cell samples, whereas MOC-31 and Ber-EP4 stained some of them.
  • Claudin-4 had a sensitivity of 69.2% for metastatic carcinomas that were not adenocarcinomas.
  • In the one hepatocellular carcinoma and the one malignant melanoma, all three stains were negative.
• The authors' conclusion: The authors concluded that claudin-4 was superior to the classical markers Ber-EP4 and MOC-31 in distinguishing metastatic carcinomas from malignant mesotheliomas and reactive mesothelial cells. They said it might be considered the first choice for this differential diagnosis in effusion cytology.
• Limitations the authors state:
  • Claudin-4 had relatively low sensitivity for carcinomas other than adenocarcinoma, so the authors said additional markers would be needed.
  • The authors noted that the high share of adenocarcinomas among the carcinomas may reflect sampling bias.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Claudin-4, Ber-EP4, MOC-31, Cytology, Differential Diagnosis, Carcinoma, Mesothelioma, Reactive Mesothelial Hyperplasia.

Related studies

• Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology — V.Y. Jo, E.S. Cibas, et al. (2014)
• Utility of Claudin-4 versus BerEP4 and B72.3 in pleural fluids with metastatic lung adenocarcinoma — A. Patel, A.C. Borczuk, et al. (2020)
• The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions — C. Sadullahoglu, D. Nart, et al. (2017)
• Diagnostic usefulness of EMA, IMP3, and GLUT-1 for the immunocytochemical distinction of malignant cells from reactive mesothelial cells in effusion cytology using cytospin preparations — K. Ikeda, G. Tate, et al. (2011)
• IMP3/L523S, a novel immunocytochemical marker that distinguishes benign and malignant cells: the expression profiles of IMP3/L523S in effusion cytology — K. Ikeda, G. Tate, et al. (2010)
• Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens — M. Vojtek, M.D. Walsh, et al. (2019)

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