Ribonucleotide reductase immunoreactivity in adenocarcinoma cells and malignant or reactive mesothelial cells in serous effusions

Our plain-English summary of Ribonucleotide reductase immunoreactivity in adenocarcinoma cells and malignant or reactive mesothelial cells in serous effusions, by H. Okamura, T. Kamei, N. Sakuma, et al (Acta Cytologica, 2003).

The study

• Authors: H. Okamura, T. Kamei, N. Sakuma, N. Hanai, T. Ishihara
• Journal: Acta Cytologica
• Published: 2003;47(2):209-15
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Ribonucleotide reductase (RNR) is a cytoplasmic enzyme that is essential for DNA synthesis. Its activity is strongly associated with cell proliferation. We assessed the value of immunostaining for RNR in distinguishing between reactive mesothelia (RM), malignant mesotheliomas (MM) and adenocarcinomas (AC) in serous effusions.

Study Design: Cytocentrifuged cell smears of serous effusions from 38 RM, 10 MM and 36 AC were immunostained with the monoclonal antibody KM1054 raised against the R2 subunit of RNR (RNR-R2) using the labeled streptavidin-biotin method. Quantitative RNR-R2 values were determined by counting the percentages of immunoreactive cells.

Results: RNR-R2 immunostaining was confined to the cytoplasm. The median RNR-R2 value was 1.4% (range, 0-7.9%) for RM, 11.2% (4.1-15.3%) for MM and 12.1% (2.0-40.6%) for AC. Significant differences in RNR-R2 values were found for both AC versus RM (P < .001) and MM versus RM (P = .009). There was no difference between AC and MM (P = .26). An RNR-R2 value > or = 7% was found in 30 of 36 AC, 8 of 10 MM and 2 of 38 RM.

Conclusion: RNR-R2 immunostaining can be useful as an adjunct for differentiating AC or MM from RM in serous effusions.

In plain English

This laboratory study from Japan tested whether staining fluid samples for part of an enzyme linked to cell division could help tell apart three kinds of cells. The marker was the R2 subunit of ribonucleotide reductase (RNR-R2). The fluid came from around the lungs, abdomen or heart (serous effusions), and the three cell types were reactive (benign) mesothelial cells, malignant mesothelioma cells and adenocarcinoma cells. The authors stained cell smears from 84 effusions: 38 reactive mesothelia, 10 malignant mesotheliomas and 36 adenocarcinomas. They then counted the percentage of stained cells. The median was 1.4% for reactive mesothelia, 11.2% for mesothelioma and 12.1% for adenocarcinoma. Both mesothelioma and adenocarcinoma differed significantly from reactive mesothelia. There was no significant difference between mesothelioma and adenocarcinoma (P = .26). Using a value of 7% or more to indicate malignancy, specificity was 94.7% and sensitivity 82.6%. The authors concluded that the stain is a potentially useful adjunct for separating malignant from benign cells. Because its sensitivity is relatively limited, they said it should always be interpreted together with cell appearance and clinical findings. The article does not discuss asbestos exposure.

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: immunostaining of cytology smears from serous effusions, with blinded counting of stained cells
• Who was studied: 84 serous effusions (39 pleural, 41 peritoneal, 4 pericardial): 36 adenocarcinoma, 10 malignant mesothelioma (eight epithelial, two biphasic) and 38 reactive mesothelia. Authors are from Yamaguchi, Japan. Collection dates are not given.
• Exposure: No asbestos or other exposure was studied. The study evaluated a laboratory stain (monoclonal antibody KM1054 against RNR-R2).
• Main results:
  • Adenocarcinoma: RNR-R2 values ranged from 2.0% to 40.6%, median 12.1%
  • Malignant mesothelioma: RNR-R2 values ranged from 4.1% to 15.3%, median 11.2%
  • Reactive mesothelia: RNR-R2 values ranged from 0 to 7.9%, median 1.4%
  • Adenocarcinoma versus reactive mesothelia was a statistically significant difference (P<.001)
  • Malignant mesothelioma versus reactive mesothelia was a statistically significant difference (P = .009)
  • No significant difference between adenocarcinoma and malignant mesothelioma (P = .26)
  • A value of 7% or more was found in 30 of 36 adenocarcinomas, 8 of 10 mesotheliomas and 2 of 38 reactive mesothelia
  • With 7% or more taken to indicate malignancy, specificity for identifying malignant cells (adenocarcinoma and mesothelioma) was 94.7%, sensitivity 82.6%, positive predictive value 95.0% and negative predictive value 81.8%
• The authors' conclusion: The authors concluded that RNR-R2 immunostaining is a potentially useful adjunct for differentiating malignant cells (adenocarcinoma or mesothelioma) from benign reactive mesothelial cells in serous effusions. They said it may not be helpful for telling adenocarcinoma from mesothelioma.
• Limitations the authors state:
  • The stain has relatively limited sensitivity for detecting malignancy, so the authors said it should always be interpreted together with cell appearance and clinical observation
  • Effusion samples almost always contain mixed cell populations, so cell appearance must be evaluated at the same time to choose which cells to count
  • Differences in methods and interpretation make it difficult to compare these values with those from other proliferation markers in other studies

Topics

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

Medical terms in this study, explained in our Lexicon: Adenocarcinoma, Reactive Mesothelial Cells, Malignant Mesothelioma, Monoclonal Antibody.

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• 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)
• 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)
• 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)
• Utility of HBME-1 immunostaining in serous effusions — V. Ascoli, C. Carnovale-Scalzo, et al. (1997)
• Diagnostic value of monoclonal antibody B72.3 in detecting adenocarcinoma cells in serous effusions — A.F. Lauritzen (1989)

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