The value of anti-calretinin antibody in the differential diagnosis of normal and reactive mesothelia versus metastatic tumors in effusion cytology

Our plain-English summary of The value of anti-calretinin antibody in the differential diagnosis of normal and reactive mesothelia versus metastatic tumors in effusion cytology, by H. Nagel, B. Hemmerlein, I. Ruschenburg, et al (Pathology, Research and Practice, 1998).

The study

• Authors: H. Nagel, B. Hemmerlein, I. Ruschenburg, K. Hüppe, M. Droese
• Journal: Pathology, Research and Practice
• Published: 1998;194(11):759-64
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In effusion cytology the distinction of reactive mesothelia from metastatic carcinoma cells may be a diagnostic challenge. Immunocytochemistry using antibodies suitable to detect epithelial cells must be considered carefully due to limited sensitivity and specificity of these antibodies. Efficient results in histological differential diagnosis of malignant mesothelioma versus lung-adenocarcinoma applying a novel antiserum against the calcium binding protein calretinin inspirated us to investigate the value of anti-calretinin antibody in effusion cytology combined with an epithelial marker. Cytoslides prepared by cytocentrifugation from 42 malignant and 65 reactive effusion specimens were immunostained using antibodies against calretinin and the epithelial marker Ber-EP4. Positive immunoreaction for calretinin in normal and reactive mesothelial cells was noted in 93% of the cases, whereas immunoreaction for calretinin was completely negative in the metastatic cells in 95% of the malignant effusions. Metastatic carcinoma cells were detected with anti-Ber-EP4 in 83% of malignant effusions. Non-specific positive reactions for Ber-EP4 in single mesothelial cells were observed in 16% of all cases and, moreover, frequently with macrophages or neutrophilic granulocytes. Our results demonstrate high sensitivity and specificity of anti-calretinin antibody for mesothelial cells in effusion specimens. They support its application to improve the diagnostic reliability of epithelial markers, especially because anti-calretinin antibody could be helpful in the assessment of false positive and false negative reactions of epithelial markers.

In plain English

This study, from Georg-August-University of Göttingen, Germany, tested whether an antibody against the protein calretinin helps tell normal and reactive mesothelial cells (the cells lining body cavities) from cancer cells that have spread into body fluids. Of 131 fluid specimens received from October to December 1997, 107 specimens from 102 patients were analyzed: 65 benign or reactive and 42 containing metastatic tumors, mostly carcinomas. No mesothelioma cases were included, and the article does not discuss asbestos exposure. Calretinin stained mesothelial cells in 100 of 107 specimens (93%) and stayed negative in the tumor cells of 40 of 42 malignant specimens (95%). A second marker, Ber-EP4, detected tumor cells in 34 of 41 metastatic adenocarcinomas (83%). It also stained single benign mesothelial cells in 17 specimens (12 benign, 5 malignant). It frequently stained macrophages weakly; the article describes neutrophil staining as common in one passage and rare in another. The authors concluded that calretinin is a sensitive and specific indicator of normal and reactive mesothelial cells in effusion cytology and may help recognize false positive or false negative Ber-EP4 results.

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 of immunostaining on all serous effusion specimens received over a three-month period
• Who was studied: 131 effusion specimens submitted to the Department of Cytopathology, Georg-August-University of Göttingen, from October to December 1997. 24 were excluded, leaving 107 specimens (60 pleural effusions, 45 ascitic fluids, 2 pericardial effusions) from 102 patients (63 female, 39 male). 65 were benign/reactive and 42 malignant: 11 breast, 9 ovarian, 8 pulmonary adenocarcinomas, 1 colon, 3 gastric, 1 renal cell carcinoma, 1 malignant melanoma and 8 adenocarcinomas not otherwise specified. No mesothelioma cases were included.
• Exposure: No asbestos or other environmental exposure was studied. The 'exposure' was immunostaining of cell preparations with a polyclonal antibody against calretinin and a monoclonal antibody against the epithelial marker Ber-EP4.
• Main results:
  • Calretinin stained the majority of mesothelial cells clearly positive in 100 of 107 specimens (93%), benign and malignant combined.
  • Well preserved mesothelial cells did not stain for calretinin in 7 specimens (7%).
  • Calretinin did not stain metastatic tumor cells in 40 of 42 malignant effusions (95%).
  • In the remaining two malignant effusions, single tumor cells stained for calretinin. The Results text names these as one breast and one ovarian carcinoma; the table and Discussion name one ovarian and one lung carcinoma.
  • Ber-EP4 detected tumor cells in 34 of 41 metastatic adenocarcinomas (83%). The melanoma was negative, as expected.
  • Ber-EP4 gave false positive staining of single benign mesothelial cells in 12 benign and 5 malignant effusions (17 of 107, given as 16% in the Discussion).
  • The Results section reports that Ber-EP4 reacted weakly positive in many cases with macrophages and neutrophilic granulocytes, particularly in ascitic fluid from liver cirrhosis.
  • The Discussion distinguishes the two cell types: weak nonspecific Ber-EP4 staining was frequent in macrophages and rare in neutrophil granulocytes.
  • In the 7 adenocarcinoma cases negative for Ber-EP4, calretinin staining helped show that the Ber-EP4 result was falsely negative.
• The authors' conclusion: The authors concluded that calretinin is a sensitive and specific indicator of normal and reactive mesothelial cells in effusion cytology. They wrote that it helps detect proliferating mesothelial cells and may probably recognize false positive or false negative results of epithelial markers such as Ber-EP4.

Topics

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

Medical terms in this study, explained in our Lexicon: Calretinin, Differential Diagnosis, Cytology, Carcinoma, Mesothelioma, Adenocarcinoma, Ber-EP4, Reactive Mesothelial Hyperplasia.

Related studies

• Comparison of antibodies to HBME-1 and calretinin for the detection of mesothelial cells in effusion cytology — P.A. Fetsch, A. Simsir, et al. (2001)
• Calretinin. A selective marker of normal and neoplastic mesothelial cells in serous effusions — M.C. Barberis, M. Faleri, et al. (1997)
• E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma — M.P. Leers, M.M. Aarts, et al. (1998)
• Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura — P.M. Cury, D.N. Butcher, et al. (2000)
• Immunocytochemical staining of serous effusions with the monoclonal antibody Ber-EP4 — M. De Angelis, I.D. Buley, et al. (1992)
• 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)

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