Usefulness of Claudin 4 in the cytological diagnosis of serosal effusions

Our plain-English summary of Usefulness of Claudin 4 in the cytological diagnosis of serosal effusions, by S. Lonardi, C. Manera, R. Marucci, et al (Diagnostic Cytopathology, 2011).

The study

• Authors: S. Lonardi, C. Manera, R. Marucci, A. Santoro, L. Lorenzi, F. Facchetti
• Journal: Diagnostic Cytopathology
• Published: 2011;39(5):313-7
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The identification of metastatic cells in serous effusions has prognostic and therapeutic implications, thus leading to a continuous search for improvement of the existing diagnostic procedures, including immunocytochemistry. To evaluate the usefulness of an antibody recognizing the tight junction-associated protein Claudin 4 in detecting metastatic tumor cells and in the differential with reactive and neoplastic mesothelium, we stained 345 cases of benign and neoplastic serous effusions obtained from pleura, peritoneum, and pericardium. Two-hundred and twenty-eight of 230 cases (99.1%) of epithelial metastasis of different origin were strongly stained by anti-Claudin 4, whereas all cases of reactive mesothelitis (78) and malignant mesothelioma (37) were negative. With the exception of a single case of ovarian carcinoma hypercalcemic-type, all tumors originating from the anatomical sites that most frequently metastasize to the serosae, including lung (61), breast (23), female genital tract (67), gastrointestinal tract (27), and peritoneum (6), were found to be positive. Claudin 4 was also extremely useful in detecting single-tumor cells dispersed among heavy inflammatory reaction. Because of its high sensitivity (99.1%) and specificity (100%), Claudin 4 might be used as an ideal "single-shot" marker for the identification of metastatic epithelial cells in serous effusions.

Copyright © 2010 Wiley-Liss, Inc.

In plain English

This laboratory study from the Department of Pathology at Spedali Civili Brescia, Italy, tested whether a stain for the protein Claudin 4 could help pathologists tell cancer cells that had spread from elsewhere apart from mesothelial cells in fluid collected from around the lungs (pleura), abdomen (peritoneum) and heart (pericardium). The authors stained 345 fluid smears: 154 pleural, 170 peritoneal and 21 pericardial. The stain marked 228 of 230 samples (99.1%) containing spread epithelial cancers from sites including lung, ovary, breast, gastrointestinal tract and pancreas. The two unstained cancer samples were a small-cell undifferentiated carcinoma of the ovary, hypercalcemic type, and one of three hepatocarcinomas (liver cancers). All 78 samples of reactive mesothelitis and all 37 malignant mesotheliomas were negative. The authors reported a specificity of 100% and a sensitivity of 99.1%. They found the stain particularly helpful for spotting single tumor cells. The authors concluded that Claudin 4 appears to be an ideal marker to assist diagnosis of these fluids, used together with a mesothelial marker such as calretinin. The article does not discuss 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: Diagnostic laboratory study: immunostaining (anti-Claudin 4 antibody) of stored cytology smears of body-cavity fluid with known diagnoses
• Who was studied: 345 fluid smears (154 pleural, 170 peritoneal, 21 pericardial) at the Department of Pathology, Spedali Civili Brescia, Italy. There were 230 metastatic epithelial cancers, 78 reactive mesothelitis and 37 malignant mesotheliomas (30 pleural, 7 peritoneal). Biopsy correlation was available in 212 of 267 tumor cases. 97 specimens had been used in the authors' previous study. Collection dates were not given.
• Exposure: Not applicable: the study did not examine asbestos or any other exposure. What was tested was a stain using a monoclonal antibody against Claudin 4 applied to the fluid smears.
• Main results:
  • Metastatic epithelial cancers: Claudin 4 strongly stained 228 of 230 samples (99.1%).
  • Reactive mesothelitis (78 samples) and mesothelioma (37 samples): all were negative for Claudin 4.
  • Malignant mesothelioma samples: 30 were pleural and 7 were peritoneal. All 37 were negative.
  • Overall, the authors reported specificity of 100% and sensitivity of 99.1% for Claudin 4.
  • Negative cancer samples: the two unstained cancer samples were a small-cell undifferentiated carcinoma of the ovary, hypercalcemic type, and a hepatocarcinoma (one of three hepatocarcinoma cases).
  • Cancers of unknown origin: all 36 samples expressed Claudin 4.
  • Positive cancer samples: in some, tumor cells occurred mainly as single scattered cells, and the stain was particularly helpful for identifying them.
• The authors' conclusion: The authors concluded that Claudin 4 appears to be an ideal marker to assist the immunocytochemical diagnosis of serous effusions, especially when only a limited number of stains can be applied. They suggested using it together with a positive mesothelial marker such as calretinin.
• Limitations the authors state:
  • Some inflammatory and mesothelial cells contained small dots of staining inside the cell. The authors could not rule out that this was genuine binding but treated it as nonspecific.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Mesothelium, Pleura, Peritoneum, Pericardium, Metastasis, Mesothelioma, Carcinoma.

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)
• Utility of HBME-1 immunostaining in serous effusions — V. Ascoli, C. Carnovale-Scalzo, et al. (1997)
• Diagnostic problems in serous effusions — C.W. Bedrossian (1998)
• Value of immunocytochemistry in the study of malignant effusions — M.R. Mason, C.W. Bedrossian, et al. (1987)
• MMP-7 is a highly specific negative marker for benign and malignant mesothelial cells in serous effusions — B. Davidson, H.T. Stavnes, et al. (2016)
• Detection of cancer cells in effusions from patients diagnosed with gynaecological malignancies. Evaluation of five epithelial markers — B. Davidson, B. Risberg, et al. (1999)

Browse more research in Diagnostic Cytopathology, or return to medical research.