Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The M.D. Anderson experience and a critical review of the literature

Our plain-English summary of Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The M.D. Anderson experience and a critical review of the literature, by N.G. Ordóñez (American Journal of Clinical Pathology, 1998).

The study

• Author: N.G. Ordóñez
• Journal: American Journal of Clinical Pathology
• Published: 1998;109(1):85-9
• Type of article: Review
• Cited by: 80 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Although most studies have indicated that Ber-EP4 immunostaining can assist in differentiating epithelial pleural mesotheliomas from adenocarcinomas that metastasize to the pleura, the percentage of positive cases has varied greatly among different studies. Authors of a recent publication concluded that Ber-EP4 has no diagnostic utility in separating these conditions. To determine whether Ber-EP4 has any value in distinguishing mesothelioma from adenocarcinoma, 70 formalin-fixed epithelial pleural mesotheliomas, 20 pulmonary adenocarcinomas, 59 nonpulmonary adenocarcinomas, 4 squamous cell carcinomas of the lung, 6 transitional cell carcinomas, and 31 adenocarcinomas of unknown origin that metastasized to the pleura were stained with this antibody. Reactivity was observed in 18 (26%) of 70 mesotheliomas and in all 20 (100%) of the pulmonary adenocarcinomas, in 55 (93%) of the 59 nonpulmonary adenocarcinomas, in 4 (100%) of 4 squamous cell carcinomas of the lung, in 4 (67%) of 6 transitional cell carcinomas, and in 26 (84%) of 31 adenocarcinomas of unknown origin that metastasized to the pleura. The staining in the mesotheliomas was focal and restricted to a limited number of cells, in contrast with staining in the pulmonary adenocarcinomas in which it was invariably diffuse. The extent of the staining in the nonpulmonary adenocarcinomas and the metastatic adenocarcinomas of unknown origin was less consistent--negative or focal in some cases and diffuse in others. Therefore, while Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas, its value in distinguishing mesotheliomas from other tumors metastatic to the pleura is more limited and depends largely on the site of origin of the metastatic tumor.

In plain English

This article from the M.D. Anderson Cancer Center tested whether a laboratory stain, the Ber-EP4 antibody, helps pathologists tell epithelial pleural mesothelioma apart from adenocarcinoma. It also reviewed earlier published studies. It did not examine asbestos exposure. The author stained archived tissue from 70 epithelial pleural mesotheliomas and from a range of other cancers. Staining appeared in 18 of the 70 mesotheliomas (26%), but in each of these it involved at most 25% of the tumor cells. All 20 lung adenocarcinomas stained diffusely, in more than 75% of cells. Among adenocarcinomas from other organs, 5 of 9 kidney cancers stained, as did every breast, ovary, colon and prostate case tested. Of 31 adenocarcinomas of unknown origin that had spread to the pleura, 26 stained. In the published studies reviewed, reported staining of mesotheliomas ranged from 0% to 88%. The author concluded that Ber-EP4 can help separate epithelial pleural mesothelioma from lung adenocarcinoma. The author added that weak or negative staining does not always separate mesothelioma from cancers that spread from outside the lung, and advised using the stain only when an additional marker is needed.

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 immunostaining study of archived tumor tissue, combined with a review of published studies on the Ber-EP4 antibody
• Who was studied: Tissue from the pathology files of the University of Texas M.D. Anderson Cancer Center: 70 epithelial pleural mesotheliomas, 20 primary lung adenocarcinomas, 59 nonpulmonary adenocarcinomas (20 breast, 20 ovary, 9 renal cell, 5 colon, 5 prostate), 31 adenocarcinomas of unknown origin that had spread to the lung and pleura, 4 primary lung squamous cell carcinomas, and 6 transitional cell carcinomas that had spread to the lung. No dates are given.
• Exposure: Not an asbestos exposure study. What was tested was staining of formalin-fixed, paraffin-embedded tissue sections with the Ber-EP4 mouse monoclonal antibody. Staining was graded by the percentage of reactive cells.
• Main results:
  • Epithelial pleural mesotheliomas: 18 of 70 (26%) stained with Ber-EP4, along the cell membranes.
  • Among the 18 stained mesotheliomas, 15 were graded 1+ (1% to 25% of cells reactive). The remaining 3 had fewer than 1% of cells reactive.
  • Lung adenocarcinomas: all 20 showed diffuse staining, with more than 75% of cells positive.
  • Nonpulmonary adenocarcinomas: staining was seen in 5 of 9 from the kidney, 5 of 5 from the colon, 20 of 20 from the ovary, 20 of 20 from the breast, and 5 of 5 from the prostate.
  • Adenocarcinomas of unknown origin that had spread to the pleura, a separate group from the nonpulmonary adenocarcinomas: 26 of 31 (84%) stained.
  • Other cancers: 4 of 4 lung squamous cell carcinomas and 4 of 6 metastatic transitional cell carcinomas stained.
  • Literature review: across the published studies the author compiled, reported Ber-EP4 staining of epithelial mesotheliomas ranged from 0% to 88%.
  • Literature review: in three earlier studies that used cell blocks from fluid samples or fine-needle aspiration specimens rather than tissue, reported staining of lung adenocarcinomas was 81%, 56%, and 33%.
  • Literature review: in pooled published data, 17% of hepatocellular carcinomas (1 of 6) and 36% of renal cell carcinomas (12 of 33) stained with Ber-EP4.
• The authors' conclusion: The author concluded that Ber-EP4 can help separate epithelial pleural mesothelioma from lung adenocarcinoma. The reason given is that lung adenocarcinoma almost always stains strongly and diffusely, while mesothelioma staining is negative or weak and focal. Its value for other tumors that spread to the pleura is more limited.
• Limitations the authors state:
  • The author states that in small pleural biopsy specimens the staining can be hard to interpret, especially when only single cells are positive.
  • The author notes that reactive (non-cancerous) lung alveolar cells can stain with Ber-EP4 and may be hard to tell apart from tumor cells.
  • The author states that weak or negative staining does not always distinguish pleural mesothelioma from cancers that spread from outside the lung.
  • Because of these limitations, the author states that Ber-EP4 should be used only when an additional marker is needed, not as part of the routine set of markers for diagnosing mesothelioma.

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, Pleural Mesothelioma, Adenocarcinoma, Metastasis, Pleura, Mesothelioma, Squamous Cell Carcinoma, Carcinoma.

Related studies

• Value of the MOC-31 monoclonal antibody in differentiating epithelial pleural mesothelioma from lung adenocarcinoma — N.G. Ordóñez (1998)
• Ber-EP4 for differentiating adenocarcinoma from reactive and neoplastic mesothelial cells in serous effusions. Comparison with carcinoembryonic antigen, B72.3 and Leu-M1 — M.E. Bailey, R.W. Brown, et al. (1996)
• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, et al. (2001)
• Diagnostic value of monoclonal antibody B72.3 in detecting adenocarcinoma cells in serous effusions — A.F. Lauritzen (1989)
• Monoclonal antibody SM047 as an immunohistochemical marker of ovarian adenocarcinoma — W.G. McCluggage, P. Maxwell, et al. (2001)
• Role of immunohistochemistry in differentiating epithelial mesothelioma from adenocarcinoma. Review and update — N.G. Ordóñez (1999)

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