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?

Our plain-English summary of 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?, by F. Kimura, J. Kawamura, J. Watanabe, et al (Diagnostic Cytopathology, 2010).

The study

• Authors: F. Kimura, J. Kawamura, J. Watanabe, S. Kamoshida, K. Kawai, I. Okayasu, S. Kuwao
• Journal: Diagnostic Cytopathology
• Published: 2010;38(3):161-7
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this study was to evaluate whether immunocytochemical expressions of proliferation markers, such as minichromosome maintenance protein 7 (MCM 7), topoisomerase IIalpha (topo IIalpha), and Ki-67, in reactive mesothelial cells and malignant cells obtained from cavital fluids could be useful for their differential diagnosis. Samples diagnosed as reactive mesothelial cells (14 cases) or malignant tumors (28 cases) in cavital fluids were examined. Immunocytochemical staining of MCM 7, topo IIalpha, and Ki-67 was performed with the universal immunoperoxidase polymer method. In reactive mesothelial cells, MCM 7 was stained in a fine granular pattern and its distribution was uniform in the nuclei. Topo IIalpha and Ki-67 were stained in a coarse granular pattern and the distributions were the same as MCM 7. In contrast, in malignant cells, MCM 7 was stained in an irregular and fine granular pattern, and topo IIalpha and Ki-67 were stained in a uniform and coarse granular pattern. Labeling indices of MCM 7 (cut-off value; 30%, sensitivity; 100%, and specificity; 100%), topo IIalpha (cut-off value; 15%, sensitivity; 89.3%, and specificity; 92.9%) and Ki-67 (cut-off value; 30%, sensitivity; 64.3%, and specificity; 92.9%) of malignant cells were significantly higher than those of reactive mesothelial cells. MCM 7, topo IIalpha, and Ki-67 are different types of cell proliferation markers. MCM 7 and topo IIalpha, in particular, could be reliable tools for differential diagnosis between reactive mesothelial cells and malignant cells.

In plain English

This study, from Higashiyamato Hospital in Tokyo, Japan, tested whether three markers of dividing cells (MCM 7, topoisomerase IIalpha and Ki-67) could help tell reactive (non-cancerous) mesothelial cells from cancer cells in body-cavity fluid samples. The authors stained 42 fluid samples: 14 with reactive mesothelial cells and 28 with cancer. The cancers were 3 malignant mesotheliomas (2 pleural, 1 peritoneal), 21 adenocarcinomas, 1 squamous cell carcinoma and 3 small cell lung carcinomas. The article did not report on asbestos exposure. For all three markers, the share of stained cells was significantly higher in the cancer samples than in the reactive samples. For MCM 7 the averages were 59.5% and 9.8%. At a 30% cut-off, MCM 7 had 100% sensitivity and 100% specificity in these samples. Topoisomerase IIalpha at 15% gave 89.3% and 92.9%, and Ki-67 at 30% gave 64.3% and 92.9%. The authors concluded that MCM 7 and topoisomerase IIalpha could be reliable tools for this distinction, used together with the cells' appearance. They described their retrospective data as a basis for a prospective study.

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: Retrospective laboratory study of diagnostic markers (immunocytochemical staining of cavity-fluid cytology samples), with cut-off values chosen from ROC curves
• Who was studied: 42 cavity-fluid samples from 24 women and 18 men (average age 64.9 years). There were 14 cases of reactive mesothelial cells and 28 malignant cases: 3 malignant mesothelioma (2 pleura, 1 peritoneum), 21 adenocarcinoma (14 lung, 6 ovary, 1 uterus), 1 squamous cell carcinoma of the lung and 3 small cell lung carcinoma. Diagnoses were established by histology at Higashiyamato Hospital, Tokyo, between January 2006 and March 2007. Samples with fewer than 500 cells were excluded.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The factors examined were staining for three cell proliferation markers: MCM 7, topoisomerase IIalpha and Ki-67. Each was measured as a labeling index, the percentage of stained nuclei among about 500 to 1,000 cells.
• Main results:
  • Labeling indices of all three markers were significantly higher in the 28 malignant cases than in the 14 reactive mesothelial cases (P less than 0.0001 for MCM 7 and topo IIalpha; P = 0.0003 for Ki-67, Mann-Whitney U-test).
  • Mean labeling indices (with standard deviation) in reactive mesothelial cells were 9.8 (6.6) for MCM 7, 5.4 (4.3) for topo IIalpha and 15.6 (8.8) for Ki-67.
  • Mean labeling indices (with standard deviation) in all malignant cases were 59.5 (15.3) for MCM 7, 30.3 (9.2) for topo IIalpha and 36.5 (13.0) for Ki-67.
  • The best cut-off for MCM 7, a labeling index of 30%, gave sensitivity of 100% and specificity of 100% for telling reactive mesothelial cells from malignant cells.
  • The best cut-offs for topo IIalpha (15%) and Ki-67 (30%) gave sensitivity of 89.3% and 64.3%, and specificity of 92.9% and 92.9%, respectively.
  • Among tumor types, MCM 7 labeling was highest in small cell lung carcinoma (92.9), followed by adenocarcinoma (56.2), squamous cell carcinoma (54.1) and malignant mesothelioma (51.3); this difference was significant (P less than 0.05). Differences by tumor type were not significant for topo IIalpha (P = 0.27) or Ki-67 (P = 0.12).
  • Staining patterns differed. In reactive mesothelial cells MCM 7 stained in a fine granular, uniform pattern; in malignant cells MCM 7 stained in an irregular, fine granular pattern.
• The authors' conclusion: The authors concluded that MCM 7 and topo IIalpha in particular could be reliable tools for distinguishing reactive mesothelial cells from malignant cells, and that MCM 7 was the better marker. They also wrote that morphology remains fundamental and should be considered together with these markers.
• Limitations the authors state:
  • The authors described the study as retrospective and said a prospective study is needed to establish the markers' usefulness.
  • Squamous cell carcinoma was left out of the comparison between tumor types because there was only one case.
  • When there are too few suspicious cells, proliferation markers cannot be assessed, and tumor-specific or tissue-specific markers would be useful instead.

Topics

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

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