Diagnostic and prognostic value of Ki67 proliferation fraction in serous effusions

Our plain-English summary of Diagnostic and prognostic value of Ki67 proliferation fraction in serous effusions, by A. Schönherr, M. Bayer, A. Böcking (Cellular Oncology, 2004).

The study

• Authors: A. Schönherr, M. Bayer, A. Böcking
• Journal: Cellular Oncology
• Published: 2004;26(1-2):57-62
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The Ki67 proliferation rate of mesothelial cells was determined in 20 effusions due to malignant mesotheliomas and in 20 non-neoplastic effusions, to investigate if this marker may be useful to identify neoplastic mesothelioma cells and if there is a correlation between proliferation rate and survival time. Using the ABC-method, effusions were immunostained and the marker Ki67 was evaluated quantitatively. Ki67 proliferation fraction showed rates from 2.3% to 70% in malignant mesothelioma cells and from 1.8% to 25.5% in reactive mesothelial cells. A significant difference was found (p=0.05) between those two groups. Assuming a threshold at 26%, a sensitivity of 25% and specificity of 100% resulted. Yet, due to its low sensitivity this marker seems not to be useful for differential diagnosis. Plotting surviving period against Ki67 proliferation fraction a correlation was observed which was not significant. Long term survivors (>28 month) showed proliferation rates below 3.8%. Unexpectedly a highly significant difference (p=0.001) between Ki67 proliferation rates of mesothelial cells from patients with malignant tumors other than mesothelial origin (7.0% to 25.5%) and mesothelial cells of patients without any malignant disease (1.8% to 16.3%) were observed. Setting a threshold at 10% for identification of a malignant disease, a sensitivity of 77.8% and specificity of 90.9% resulted.

In plain English

This laboratory study came from the Institute of Cytopathology in Düsseldorf, Germany. It measured Ki67, a marker of dividing cells, in mesothelial cells from 40 fluid samples (effusions) taken from the pleural, pericardial or peritoneal cavities and examined from 1997 to 2000. Twenty samples contained malignant epithelial mesothelioma cells, confirmed by tissue examination. Twenty contained no tumor cells. The article does not report asbestos exposure. Ki67 rates were 3.5% to 70% (average 22.4%) in mesothelioma samples and 1.8% to 25.5% (average 10.8%) in tumor-cell-negative samples, which the authors reported as a significant difference (p = 0.05). A cut-off of 26% identified 25% of mesotheliomas, with a specificity of 100%. Among tumor-cell-negative samples, patients with cancers other than mesothelioma had higher rates than patients without cancer (p = 0.001). In mesothelioma patients, survival tended to be longer when rates were lower, but this was not statistically significant (p = 0.079). The authors concluded that Ki67 is not suitable for telling mesothelioma cells from reactive mesothelial cells because of its low sensitivity. They called for more patients and further studies.

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 and prognostic laboratory study of Ki67 immunostaining in routinely examined effusion samples
• Who was studied: 40 effusions (pleural, pericardial or peritoneal). Twenty were tumor-cell positive with malignant epithelial mesothelioma, verified histologically. Twenty were tumor-cell negative and came from patients with various other conditions, nine of them cancers other than mesothelioma. Samples came from the University Hospital of Düsseldorf and surrounding hospitals, 1997 to 2000.
• Exposure: No asbestos or fiber exposure is reported. The study examined Ki67 proliferation fraction (MIB-1 antibody, ABC method) in mesothelial and mesothelioma cells.
• Main results:
  • Mesothelioma effusions had Ki67 rates of 3.5% to 70% (average 22.4%). Tumor-cell-negative effusions had rates of 1.8% to 25.5% (average 10.8%). The authors reported the difference as significant (p = 0.05), and the two groups overlapped in the lower range.
  • At a 26% threshold, recognition of malignant mesothelioma had a specificity of 100% and a sensitivity of 25%. Rates above 26% occurred in every fourth mesothelioma sample and in no tumor-cell-negative sample.
  • Within the tumor-cell-negative effusions, mesothelial cells from patients with malignant tumors other than mesothelioma had rates of 7.0% to 25.5%. Cells from patients without malignant disease had rates of 1.8% to 16.3%. The authors reported this difference as highly significant (p = 0.001).
  • In the tumor-cell-negative group, a 10% threshold for identifying a malignant tumor other than mesothelioma gave a sensitivity of 77.8% and a specificity of 90.9%.
  • Among mesothelioma patients, survival tended to be longer as Ki67 fell (correlation coefficient minus 0.45, p = 0.079, not significant). Average survival from cytological diagnosis was 10.9 months.
  • Three mesothelioma patients lived 28, 32 and 43 months. Two of them had very low Ki67 rates (3.5% and 3.8%), and the third had a medium rate.
• The authors' conclusion: The authors concluded that Ki67 proliferation fraction in effusions is not suitable for distinguishing reactive mesothelial cells from mesothelioma cells because of its low sensitivity. They found raised rates in normal mesothelial cells of patients with other cancers and supposed a link between Ki67 and survival. In both cases they said more patients and further studies are needed before diagnostic or prognostic use.
• Limitations the authors state:
  • The authors could not exclude that chemotherapy or radiation, which some patients may have received, influenced mesothelial cell proliferation.
  • Patients were in different disease stages and had received different treatments.
  • More patients should be evaluated before Ki67 is used diagnostically.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Mesothelioma, Reactive Mesothelial Hyperplasia, Differential Diagnosis.

Related studies

• The diagnostic role of BAP1 in serous effusions — B. Davidson, M. Tötsch, et al. (2018)
• The Diagnostic Value of Immunohistochemistry and Biomarkers in the Diagnosis of Mesothelioma in Pleural/Peritoneal Effusions — S.M. Selvaggi (2026)
• 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)
• Significance of cell proliferation markers (Minichromosome maintenance protein 7, topoisomerase IIalpha and Ki-67) in cavital fluid cytology: can we differentiate reactive mesothelial cells from malignant cells? — F. Kimura, J. Kawamura, et al. (2010)
• 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)
• Additional techniques in serous effusions — A.G. Hanselaar (2002)

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