Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase II alpha and Ki-67

Our plain-English summary of Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase II alpha and Ki-67, by F. Kimura, I. Okayasu, H. Kakinuma, et al (Acta Cytologica, 2013).

The study

• Authors: F. Kimura, I. Okayasu, H. Kakinuma, Y. Satoh, S. Kuwao, M. Saegusa, J. Watanabe
• Journal: Acta Cytologica
• Published: 2013;57(4):384-90
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: The aim of this study was to evaluate whether the immunocytochemical expression of cell proliferation markers, such as minichromosome maintenance protein 7 (MCM 7), geminin, topoisomerase II alpha (topo IIα) and Ki-67, which are different types of cell proliferation markers, could be useful for their differential diagnosis in reactive mesothelial cells and malignant mesothelioma cells obtained from body cavity fluids.

Study Design: Samples diagnosed and later histologically confirmed as reactive mesothelial cells (39 cases) or malignant mesothelioma (32 cases) in body cavity fluids were examined. Immunocytochemical staining of MCM 7, geminin, topo IIα and Ki-67 was performed with the immunoperoxidase polymer method.

Results: Labeling indices (LIs) of MCM 7 (cutoff value 20.0%; sensitivity 100%; specificity 100%), geminin (cutoff value 4.5%; sensitivity 88.0%; specificity 70.0%), topo IIα (cutoff value 11.0%; sensitivity 88.0%; specificity 92.0%) and Ki-67 (cutoff value 15.3%; sensitivity 78.0%; specificity 79.0%) of malignant mesothelioma cells were significantly higher than those of reactive mesothelial cells.

Conclusion: LIs of MCM 7, geminin and topo IIα can be reliable tools for the differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells.

Copyright © 2013 S. Karger AG, Basel.

In plain English

This Japanese study tested whether four markers of cell division (MCM 7, geminin, topoisomerase II alpha and Ki-67) could help tell malignant mesothelioma cells apart from reactive, non-cancerous mesothelial cells in body cavity fluid samples. The authors stained fluid samples from 39 cases of reactive mesothelial cells and 32 cases of malignant mesothelioma, all confirmed by tissue examination at Kitasato University Hospital between March 1992 and January 2007. They then counted the percentage of stained cells. The article did not report the patients' asbestos exposure histories. All four markers were significantly higher in the mesothelioma cells. For example, the average MCM 7 value was 48.7% in mesothelioma cases against 5.6% in reactive cases. At a 20.0% cutoff, MCM 7 had sensitivity and specificity of 100%. The other markers were less accurate: topoisomerase II alpha 88.0% and 92.0%, geminin 88.0% and 70.0%, and Ki-67 78.0% and 79.0%. Geminin was measured in only 24 reactive cases. The authors concluded that MCM 7, geminin and topoisomerase II alpha could be reliable tools for this distinction, and cautioned that cutoff values may differ by tumor type.

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 (immunocytochemistry) on archived body cavity fluid samples with histologically confirmed diagnoses, comparing reactive mesothelial cells with malignant mesothelioma cells
• Who was studied: 71 body cavity fluid samples: 39 cases of reactive mesothelial cells and 32 cases of malignant mesothelioma, verified by histology at Kitasato University Hospital, Japan, between March 1992 and January 2007
• Exposure: Not an asbestos exposure study. The introduction discusses asbestos restrictions and latency in general, but the patients' asbestos exposure histories are not reported. The tests studied were labeling indices (percentage of stained cell nuclei) for the cell proliferation markers MCM 7, geminin, topoisomerase II alpha and Ki-67.
• Main results:
  • Mean labeling indices in reactive mesothelial cells: MCM 7 5.6, geminin 3.5, topo II alpha 4.8, Ki-67 10.4 (with standard deviations 3.0, 1.5, 2.4 and 5.0)
  • Mean labeling indices in malignant mesothelioma cases: MCM 7 48.7, geminin 15.6, topo II alpha 23.4, Ki-67 29.1 (with standard deviations 14.2, 10.4, 11.9 and 14.9)
  • All four markers were significantly higher in malignant mesothelioma cells than in reactive mesothelial cells
  • MCM 7 cutoff of 20.0% gave sensitivity and specificity of 100% for distinguishing reactive from malignant cells
  • Best cutoffs for geminin, topo II alpha and Ki-67 were 4.5, 11.0 and 15.3%, with sensitivities of 88.0, 88.0 and 78.0% and specificities of 70.0, 92.0 and 79.0%
  • Geminin was assessed in 24 of the reactive mesothelial cell cases, not all 39
  • In malignant mesothelioma, MCM 7 expression correlated positively with geminin (r = 0.62), topo II alpha (r = 0.37) and Ki-67 (r = 0.61)
• The authors' conclusion: The authors concluded that MCM 7, geminin and topo II alpha in particular could be reliable tools for distinguishing reactive mesothelial cells from malignant mesothelioma cells.
• Limitations the authors state:
  • Cutoff values may differ depending on the histological type of tumor, and cutoffs here differed from the authors' previous study
  • Labeling indices in this study were lower than in the authors' previous study, which the authors linked to different slide preparation methods

Topics

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

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Reactive Mesothelial Cells, Malignant Mesothelioma, Ki-67.

Related studies

• 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)
• Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7), Topoisomerase IIα, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma Patients Using Tissue Microarray — M. Deraco, A. Cabras, et al. (2015)
• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)
• Value of Glut-1 and Koc markers in the differential diagnosis of reactive mesothelial hyperplasia, malignant mesothelioma and pulmonary adenocarcinoma — Ö. Üçer, A.F. Dağli, et al. (2013)
• 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)
• Oncofetal protein IMP3, a new diagnostic biomarker to distinguish malignant mesothelioma from reactive mesothelial proliferation — M. Shi, A.E. Fraire, et al. (2011)

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