Ber-EP4 for differentiating adenocarcinoma from reactive and neoplastic mesothelial cells in serous effusions. Comparison with carcinoembryonic antigen, B72.3 and Leu-M1

Our plain-English summary of Ber-EP4 for differentiating adenocarcinoma from reactive and neoplastic mesothelial cells in serous effusions. Comparison with carcinoembryonic antigen, B72.3 and Leu-M1, by M.E. Bailey, R.W. Brown, D.R. Mody, et al (Acta Cytologica, 1996).

The study

• Authors: M.E. Bailey, R.W. Brown, D.R. Mody, P. Cagle, I. Ramzy
• Journal: Acta Cytologica
• Published: 1996;40(6):1212-6
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: To evaluate the efficacy of Ber-EP4 in distinguishing epithelial cells from mesothelial cells in routine cytologic preparations.

Study Design: Paraffin-embedded cell blocks of serous effusions from 32 patients (11 metastatic adenocarcinomas, 16 reactive mesothelial proliferations and 5 malignant mesotheliomas) were immunostained with Ber-EP4. For comparison, cell block preparations of adenocarcinomas and mesotheliomas were also immunostained with the most commonly applied markers of adenocarcinoma: carcinoembryonic antigen (CEA), B72.3 and Leu-M1. In addition, cytocentrifuge preparations of 14 reactive effusions and 2 metastatic adenocarcinomas were stained prospectively with Ber-EP4.

Results: All adenocarcinomas showed intense membrane staining, while all mesothelial proliferations, both benign and malignant, were negative. The Ber-EP4-positive immunostaining was remarkably clean, with very minimal nonspecific staining. CEA stained 11/11 adenocarcinomas, B72.3 stained 10/11, and Leu-M1 stained 8/11; mesotheliomas were negative with all three antibodies.

Conclusion: Ber-EP4 is at least as useful as CEA, B72.3 and Leu-M1 in the diagnosis of serous effusions. It has the advantage of high sensitivity and ease of interpretation because of the high percentage of tumor cells stained, characteristic membranous staining and lack of cross-reaction with background inflammatory cells.

In plain English

This laboratory study, from Baylor College of Medicine and Methodist Hospital in Houston, Texas, tested whether a stain called Ber-EP4 could tell adenocarcinoma cells apart from mesothelial cells in fluid from around the lungs or abdomen. The authors stained cell blocks from 32 effusions (26 pleural, 6 peritoneal): 11 metastatic adenocarcinomas, 5 malignant mesotheliomas and 16 reactive mesothelial proliferations. They also stained cytospin slides from 14 reactive effusions and 2 adenocarcinomas. They compared Ber-EP4 with three other markers: CEA, B72.3 and Leu-M1. Ber-EP4 stained all adenocarcinomas (11/11 cell blocks, 2/2 cytospins) with intense membrane staining in more than 50% of malignant cells. None of the benign or malignant mesothelial proliferations showed this membrane pattern. Occasional weak staining in fewer than 10% of cells was counted as negative. CEA stained 11/11 adenocarcinomas, B72.3 stained 10/11 and Leu-M1 stained 8/11. CEA and Leu-M1 also stained background inflammatory cells. The authors concluded that Ber-EP4 is at least as useful as these three markers. Limited material prevented some stains. 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: Laboratory diagnostic study of immunostaining: archival cell blocks of effusions, plus cytospin preparations stained prospectively
• Who was studied: 32 effusions (26 pleural, 6 peritoneal) collected at the Methodist Hospital, Houston, Texas: 11 metastatic adenocarcinomas, 16 reactive mesothelial proliferations and 5 malignant mesotheliomas. Cytospin slides were also made from 14 reactive effusions (12 pleural, 2 peritoneal) and 2 effusions with metastatic mammary adenocarcinoma. Dates of collection are not given.
• Exposure: Not an exposure study; no asbestos or fiber exposure is reported. The stains compared were Ber-EP4 and three established adenocarcinoma markers: carcinoembryonic antigen (CEA), B72.3 and Leu-M1.
• Main results:
  • Ber-EP4 stained all metastatic adenocarcinomas, 11/11 in cell blocks and 2/2 in cytospin preparations, with an intense membrane pattern
  • In the adenocarcinomas, a high percentage (more than 50%) of the cytologically malignant cells were stained by Ber-EP4
  • None of the reactive mesothelial proliferations stained with the diagnostic membranous pattern with Ber-EP4
  • In both benign and malignant mesothelial proliferations, occasional weak cytoplasmic Ber-EP4 staining was seen in fewer than 10% of cells and was interpreted as negative
  • Among the 11 adenocarcinomas, CEA was positive in 11/11 and Leu-M1 in 8/11, but both also stained many background inflammatory cells
  • B72.3 was positive in 10/11 adenocarcinomas, but a much lower percentage of malignant cells were stained
  • The malignant mesotheliomas were negative with CEA, B72.3 and Leu-M1
  • Specificity of Ber-EP4 in this study was 100%
• The authors' conclusion: The authors concluded that Ber-EP4 is at least as useful as CEA, B72.3 and Leu-M1 in the cytologic diagnosis of serous effusions. They also stated that it should be included in panels of stains.
• Limitations the authors state:
  • Repeat immunostaining was not performed on the malignant mesothelioma cases because of limited material
  • The adenocarcinomas in the cytospin preparations were not stained for CEA, Leu-M1 or B72.3 because of limited material
  • Other studies found false positive rates that this study did not. The authors said their 100% specificity probably reflects their strict criteria for a positive result and the predominance of pleural fluids in their study.

Topics

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

Medical terms in this study, explained in our Lexicon: Ber-EP4, Adenocarcinoma, Mesothelial Cells, Carcinoembryonic Antigen (CEA), B72.3 (TAG-72), Cell Block, Malignant Mesothelioma, 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)
• Lung surfactant protein-A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma — N. Shijubo, Y. Honda, et al. (1995)
• Ribonucleotide reductase immunoreactivity in adenocarcinoma cells and malignant or reactive mesothelial cells in serous effusions — H. Okamura, T. Kamei, et al. (2003)
• Utility of HBME-1 immunostaining in serous effusions — V. Ascoli, C. Carnovale-Scalzo, et al. (1997)
• The distinction of adenocarcinoma from malignant mesothelioma in cell blocks of effusions: the role of routine mucin histochemistry and immunohistochemical assessment of carcinoembryonic antigen, keratin proteins, epithelial membrane antigen, and milk fat globule-derived antigen — E.S. Cibas, J.M. Corson, et al. (1987)
• Diagnostic value of monoclonal antibody B72.3 in detecting adenocarcinoma cells in serous effusions — A.F. Lauritzen (1989)

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