Utility of Claudin-4 versus BerEP4 and B72.3 in pleural fluids with metastatic lung adenocarcinoma

Our plain-English summary of Utility of Claudin-4 versus BerEP4 and B72.3 in pleural fluids with metastatic lung adenocarcinoma, by A. Patel, A.C. Borczuk, M.T. Siddiqui (Journal of the American Society of Cytopathology, 2020).

The study

• Authors: A. Patel, A.C. Borczuk, M.T. Siddiqui
• Journal: Journal of the American Society of Cytopathology
• Published: 2020;9(3):146-151
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Lung adenocarcinoma (LADC) is the most common occult primary in patients presenting with a malignant pleural effusion. Distinguishing metastatic LADC from reactive mesothelial cells (RMC) and malignant mesothelioma (MM) based on morphology alone has been a persistent diagnostic challenge in cytopathology. Claudin-4, a major functional constituent of tight junctions, has been shown to help distinguish LADC from RMC and MM in surgical specimens. Our goal was to further validate and assess the utility of Claudin-4 in comparison to BerEP4 and B72.3 in malignant effusions with a focus on metastatic LADC.

Materials And Methods: We evaluated 58 pleural effusions (40 LADC, 10 RCM, and 8 MM). Immunohistochemistry was performed using Claudin-4, Ber-EP4, and B72.3 on cell blocks. Staining patterns, quantity of tumor cells, and intensity of staining (weak, moderate, or strong) were assessed.

Results: All cases of LADC were positive for Claudin-4 with an overall sensitivity of 100% (40 of 40) and specificity of 100% (18 of 18). In addition, Claudin-4 showed the highest quantity and quality of staining with 3+ staining intensity in 73% (29 of 40) of cases, compared with 35% (14 of 40) of cases using BerEP4 and 52% (21 of 40) of cases using B72.3. The sensitivity and specificity for BerEP4 were 90% and 78%, respectively. The sensitivity and specificity for B72.3 were 87.5% and 100%, respectively.

Conclusions: In this study, Claudin-4 performed superiorly compared to BerEP4 and B72.3 in distinguishing lung adenocarcinoma from RMC or MM in pleural effusions. Our results show Claudin-4 is a useful marker for distinguishing RMC and MM from lung adenocarcinoma, with high sensitivity (100%) and specificity (100%), compatible with studies shown in the literature.

Published by Elsevier Inc.

In plain English

This retrospective laboratory study at Weill Cornell Medicine in New York tested how well three laboratory stains (Claudin-4, BerEP4 and B72.3) told lung adenocarcinoma, a lung cancer that had spread to the pleural fluid, apart from reactive mesothelial cells and malignant mesothelioma. The authors examined 58 pleural fluid samples: 40 lung adenocarcinoma, 8 malignant mesothelioma and 10 reactive mesothelial cells. Claudin-4 stained all 40 adenocarcinoma samples and none of the 18 mesothelioma or reactive samples, a sensitivity of 100% and a specificity of 100%. A dot-like staining seen in some mesothelial samples was counted as negative. BerEP4 had 90% sensitivity and 78% specificity, and it stained 3 of 8 mesothelioma samples. B72.3 had 87.5% sensitivity and 100% specificity. Strong staining appeared in 29 of 40 adenocarcinoma samples with Claudin-4, 14 of 40 with BerEP4 and 21 of 40 with B72.3. The authors concluded that Claudin-4 performed better than the other two markers and that the dot-like pattern should be interpreted with caution. The study did not look at 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 laboratory study comparing immunohistochemical stains (Claudin-4, BerEP4, B72.3) on pleural fluid cell blocks
• Who was studied: 58 pleural effusion samples at New York Presbyterian Hospital and Weill Cornell Medicine: 40 lung adenocarcinoma and 8 malignant mesothelioma (2015 to 2018), plus 10 reactive mesothelial cell cases selected from 2018 in patients with no known history of malignancy
• Exposure: The article does not study asbestos or any other exposure. It compares three laboratory stains (Claudin-4, BerEP4, B72.3) used to tell lung adenocarcinoma apart from mesothelial cells.
• Main results:
  • Claudin-4 stained all 40 lung adenocarcinoma samples and was negative in all 10 reactive mesothelial cell and all 8 malignant mesothelioma samples. That gave a sensitivity of 100% (40 of 40) and a specificity of 100% (18 of 18).
  • A dot-like cytoplasmic Claudin-4 staining was seen in 40% (4 of 10) of reactive mesothelial cell samples and 37% (3 of 8) of malignant mesothelioma samples. It was interpreted as negative.
  • BerEP4 stained 90% (36 of 40) of lung adenocarcinoma, 37.5% (3 of 8) of malignant mesothelioma and 10% (1 of 10) of reactive mesothelial cell samples. Its sensitivity was 90% and its specificity 78%.
  • B72.3 stained 87.5% (35 of 40) of lung adenocarcinoma samples and none of the reactive mesothelial cell or mesothelioma samples. Its sensitivity was 87.5%, specificity 100% and negative predictive value 78%.
  • Strong (3+) staining of lung adenocarcinoma samples was seen in 73% (29 of 40) with Claudin-4, 35% (14 of 40) with BerEP4 and 52% (21 of 40) with B72.3.
  • In lung adenocarcinoma samples, 91% to 100% of tumor cells stained in 90% (36 of 40) of cases with Claudin-4. The same was true for 22.5% (9 of 40) of cases with BerEP4 and 12.5% (5 of 40) with B72.3.
• The authors' conclusion: The authors concluded that Claudin-4 distinguished lung adenocarcinoma from malignant mesothelioma and reactive mesothelial cells with high sensitivity and specificity. They found it performed better than BerEP4 and B72.3 and said the dot-like staining pattern should be interpreted with caution. They considered adding Claudin-4 to standard practice in effusion cytology to be of high clinical utility.

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, B72.3 (TAG-72), Lung Adenocarcinoma, Pleural Effusion, Reactive Mesothelial Hyperplasia, Mesothelioma, Cytology, Immunohistochemistry.

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)
• Immunocytochemical utility of claudin-4 versus those of Ber-EP4 and MOC-31 in effusion cytology — T. Oda, S. Ogata, et al. (2016)
• Claudin 3, 4, and 15 expression in solid tumors of lung adenocarcinoma versus malignant pleural mesothelioma — S. Chaouche-Mazouni, A. Scherpereel, et al. (2015)
• Claudin-4 as a marker for distinguishing malignant mesothelioma from lung carcinoma and serous adenocarcinoma — Y. Ohta, Y. Sasaki, et al. (2013)
• The "Brescia panel" (Claudin-4 and BRCA-associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas — L. Bernardi, T. Bizzarro, et al. (2021)
• Value of PAX8, PAX2, napsin A, carbonic anhydrase IX, and claudin-4 immunostaining in distinguishing pleural epithelioid mesothelioma from metastatic renal cell carcinoma — N.G. Ordóñez (2013)

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