Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology

Our plain-English summary of Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology, by V.Y. Jo, E.S. Cibas, G.S. Pinkus (Cancer Cytopathology, 2014).

The study

• Authors: V.Y. Jo, E.S. Cibas, G.S. Pinkus
• Journal: Cancer Cytopathology
• Published: 2014;122(4):299-306
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Adenocarcinoma can be challenging to distinguish from malignant mesothelioma in effusions, and this distinction often requires ancillary studies and clinical correlation. Immunohistochemistry for claudin-4, a tight-junction-associated protein, has recently been shown to distinguish adenocarcinoma from malignant mesothelioma, mostly in surgical specimens. Our aim was to validate and assess the immunoreactivity profile of claudin-4 in a large series of malignant effusions.

Methods: We evaluated 159 malignant effusions (84 adenocarcinomas and 75 malignant mesotheliomas). Claudin-4 immunohistochemistry was performed on cell-block paraffin sections and scored for staining intensity, staining pattern (cytoplasmic versus membranous), and percentage of positive tumor cells. Appropriate positive and negative controls were used throughout.

Results: All cases of mesothelioma were negative for claudin-4 (0 of 64). Eighty-three of 84 cases of adenocarcinoma were positive (99%); 1 case of serous carcinoma was negative. Most adenocarcinomas showed strong and diffuse membranous staining (71 of 84; 84%); 12 cases (14%) showed membranous staining of moderate intensity. The overall sensitivity for adenocarcinoma was 99% (83 of 84).

Conclusions: Claudin-4 immunohistochemistry effectively distinguishes adenocarcinoma from malignant mesothelioma with high sensitivity and specificity in the evaluation of malignant effusions.

© 2014 American Cancer Society.

In plain English

This study tested whether a laboratory stain for claudin-4 could tell adenocarcinoma apart from malignant mesothelioma in samples of fluid (effusions) collected from patients. Claudin-4 is a protein the article describes as present in most epithelial cells but absent in mesothelial cells. The authors retrieved 159 malignant effusions diagnosed between 2008 and 2012 at Brigham and Women's Hospital in Boston: 84 adenocarcinomas and 75 malignant mesotheliomas. They stained the samples and scored the results. Claudin-4 was positive in 83 of 84 adenocarcinomas. The one negative case was a serous carcinoma from a patient with ovarian cancer. All 75 mesotheliomas were negative for membranous (cell-surface) staining, although 8 showed very weak staining inside the cells. Histiocytes, a type of immune cell, often showed this kind of staining too. The body of the article reported a sensitivity of 100% and a specificity of 99%. Its abstract instead gave the sensitivity for adenocarcinoma as 99%. The authors concluded that adding claudin-4 to the standard stain panel has high utility. The study is about diagnosis and did not examine asbestos exposure.

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 archived effusion specimens, testing claudin-4 immunohistochemistry
• Who was studied: 159 malignant effusions (84 adenocarcinomas, 75 malignant mesotheliomas) diagnosed 2008 to 2012, from the cytopathology files of Brigham and Women's Hospital, Boston, MA
• Exposure: Not an exposure study. What was studied was claudin-4 immunohistochemistry (a protein stain) performed on cell-block sections of the effusions. Asbestos and fiber types are not discussed.
• Main results:
  • Adenocarcinomas: 83 of 84 (99%) were positive for claudin-4. Most showed strong and diffuse membranous staining (71 of 84). The article prints this as 85% in the results section and 84% in the abstract.
  • Adenocarcinomas: the one negative case was a serous carcinoma, in pleural fluid from a patient with stage 4 primary ovarian serous carcinoma
  • Mesotheliomas: all 75 were negative for membranous claudin-4 staining; 8 showed very weak cytoplasmic staining
  • Cytoplasmic staining of histiocytes was often seen. The authors said this did not cause problems in interpretation because staining of adenocarcinomas was membranous.
  • Adenocarcinomas: five sparsely cellular cell-block sections were still positive for claudin-4
  • The article reported that claudin-4 distinguished adenocarcinoma from malignant mesothelioma with sensitivity of 100% and specificity of 99%, P less than .0001. The abstract instead states a sensitivity for adenocarcinoma of 99% (83 of 84).
• The authors' conclusion: The authors concluded that claudin-4 immunohistochemistry effectively distinguishes adenocarcinoma from malignant mesothelioma in malignant effusions, and that adding it to the standard immunohistochemical panel has high utility in challenging cases

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, Immunohistochemistry, Adenocarcinoma, Malignant Mesothelioma, Cytology, Mesothelioma, Carcinoma.

Related studies

• The diagnostic utility of D2-40, calretinin, CK5/6, desmin and MOC-31 in the differentiation of mesothelioma from adenocarcinoma in pleural effusion cytology — T.S. Hyun, M. Barnes, et al. (2012)
• Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens — M. Vojtek, M.D. Walsh, et al. (2019)
• Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma — Y. Ohta, Y. Sasaki, et al. (2013)
• Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology — T. Oda, S. Ogata, et al. (2016)
• Utility of Claudin-4 versus BerEP4 and B72.3 in pleural fluids with metastatic lung adenocarcinoma — A. Patel, A.C. Borczuk, et al. (2020)
• Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma — H. Domínguez-Malagón, A.M. Cano-Valdez, et al. (2016)

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