Use of Anti-Noxa Antibody for Differential Diagnosis between Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia

Our plain-English summary of Use of Anti-Noxa Antibody for Differential Diagnosis between Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia, by K. Kushitani, V.J. Amatya, A.S. Mawas, et al (Pathobiology, 2016).

The study

• Authors: K. Kushitani, V.J. Amatya, A.S. Mawas, Y. Miyata, M. Okada, Y. Takeshima
• Journal: Pathobiology
• Published: 2016;83(1):33-40
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: The histological differential diagnosis between epithelioid mesothelioma (EM) and reactive mesothelial hyperplasia (RMH) is not always straightforward. The aim of the present study was to search for new immunohistochemical markers to distinguish EM from RMH.

Methods: We evaluated and compared the expression of apoptosis-related genes in EM and RMH by real-time RT-PCR array analysis followed by clustering of significant gene expression. Immunohistochemical staining and statistical analysis of Noxa expression in 81 cases of EM and 55 cases of RMH were performed and compared with the utility of other previously reported antibodies such as Desmin, EMA, GLUT-1, IMP-3 and CD146.

Results: Noxa mRNA expression levels were found to be increased in EM when compared to RMH by RT-PCR array analysis. In the immunohistochemical analysis, Noxa showed sensitivity of 69.0%, specificity of 93.6% and positive predictive value of 93.0% as a positive marker of EM in distinguishing it from RMH, and these values were almost similar to IMP-3.

Conclusion: Noxa is a marker with relatively high specificity, and can be used to distinguish EM from RMH. It would be a valuable addition to the current antibody panel used for the differential diagnosis of EM and RMH.

© 2016 S. Karger AG, Basel.

In plain English

This laboratory study from Hiroshima University, Japan, looked for a new tissue stain to help pathologists tell epithelioid mesothelioma apart from reactive mesothelial hyperplasia, a non-cancerous overgrowth of the cells lining the body cavities. The authors first measured 93 apoptosis-related genes in six mesothelioma cell lines and four normal pleural tissues taken at autopsy. Thirteen genes differed significantly, and a gene called Noxa was chosen as a candidate marker. The authors then stained archived tissue from 81 patients with epithelioid mesothelioma and 55 with reactive mesothelial hyperplasia, and compared Noxa with five previously reported markers. Noxa staining was positive in 40 of 58 mesothelioma cases (69%) and in 3 of 47 hyperplasia cases (6.4%). As a marker for mesothelioma, Noxa had a sensitivity of 69.0% and a specificity of 93.6%, similar to the marker IMP-3. EMA had the highest sensitivity (100.0%). No mesothelioma case was positive only for Noxa. The authors concluded that Noxa is a useful marker that could be added to existing marker panels. They noted that Noxa's sensitivity was relatively low. The study did not examine 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: Laboratory diagnostic study: gene expression array on cell lines and normal tissue, followed by immunohistochemical staining of archived tissue samples, with sensitivity and specificity calculated for each marker
• Who was studied: Gene analysis: 6 mesothelioma cell lines and 4 parietal pleural tissues obtained at autopsy from patients without pleural lesions or malignancy. Staining: paraffin-embedded specimens from 81 patients with epithelioid mesothelioma (1990 to 2013) and 55 patients with reactive mesothelial hyperplasia (2005 to 2013), from the archives of the Department of Pathology, Hiroshima University, Japan
• Exposure: Not an exposure study. What was tested were immunohistochemical stains: Noxa compared with Desmin, EMA, GLUT-1, IMP-3 and CD146. Asbestos exposure of the patients was not studied.
• Main results:
  • In the gene analysis, 13 of 93 apoptosis-related genes differed significantly between mesothelioma cell lines and normal pleural tissues. Noxa and Survivin (BIRC5) showed the most marked difference, with higher expression in the mesothelioma cells.
  • Noxa staining was positive in 69% (40/58) of epithelioid mesothelioma cases and 6.4% (3/47) of reactive mesothelial hyperplasia cases
  • As a positive marker for epithelioid mesothelioma, Noxa had sensitivity 69.0%, specificity 93.6%, positive predictive value 93.0%, negative predictive value 71.0% and proper diagnosis rate 80.0%
  • IMP-3 gave similar values: sensitivity 67.2%, specificity 95.6%, positive predictive value 95.6%, negative predictive value 67.2%, proper diagnosis rate 78.9%
  • EMA had the highest values: sensitivity 100.0%, specificity 88.7%, positive predictive value 93.1%, negative predictive value 100.0%, proper diagnosis rate 95.5%
  • No epithelioid mesothelioma case was positive only for Noxa
  • Staining with an anti-Survivin antibody did not show a clear difference between epithelioid mesothelioma and reactive mesothelial hyperplasia (data not shown)
• The authors' conclusion: The authors concluded that Noxa is a useful marker for distinguishing epithelioid mesothelioma from reactive mesothelial hyperplasia and could be added to the existing marker panel. They also called for further research into new markers.
• Limitations the authors state:
  • Noxa (like IMP-3) had relatively low sensitivity and negative predictive value, about 70%, compared with the other markers
  • Noxa also stained inflammatory cells, so only mesothelial and mesothelioma cells were scored. Use on cytology specimens and cell blocks needs careful evaluation.

Topics

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

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Epithelioid, Mesothelioma, Reactive Mesothelial Hyperplasia, Apoptosis, Immunohistochemistry, Desmin.

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• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)

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