Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma

Our plain-English summary of Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma, by M. Kuraoka, V.J. Amatya, K. Kushitani, et al (The American Journal of Surgical Pathology, 2017).

The study

• Authors: M. Kuraoka, V.J. Amatya, K. Kushitani, A.S. Mawas, Y. Miyata, M. Okada, T. Kishimoto, K. Inai, T. Nishisaka, T. Sueda, Y. Takeshima
• Journal: The American Journal of Surgical Pathology
• Published: 2017;41(8):1045-1052
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

As there are currently no absolute immunohistochemical positive markers for the definite diagnosis of malignant epithelioid mesothelioma, the identification of additional "positive" markers that may facilitate this diagnosis becomes of clinical importance. Therefore, the aim of this study was to identify novel positive markers of malignant mesothelioma. Whole genome gene expression analysis was performed using RNA extracted from formalin-fixed paraffin-embedded tissue sections of epithelioid mesothelioma and pulmonary adenocarcinoma. Gene expression analysis revealed that disabled homolog 2 (DAB2) and Intelectin-1 had significantly higher expression in epithelioid mesothelioma compared with that in pulmonary adenocarcinoma. The increased mRNA expression of DAB2 and Intelectin-1 was validated by reverse transcriptase polymerase chain reaction of RNA from tumor tissue and protein expression was validated by Western blotting of 5 mesothelioma cell lines. The utility of DAB2 and Intelectin-1 in the differential diagnosis of epithelioid mesothelioma and pulmonary adenocarcinoma was examined by an immunohistochemical study of 75 cases of epithelioid mesothelioma and 67 cases of pulmonary adenocarcinoma. The positive rates of DAB2 and Intelectin-1 expression in epithelioid mesothelioma were 80.0% and 76.0%, respectively, and 3.0% and 0%, respectively, in pulmonary adenocarcinoma. Immunohistochemically, the sensitivity and specificity of DAB2 was 80% and 97% and those of Intelectin-1 were 76% and 100% for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma. In conclusion, DAB2 and Intelectin-1 are newly identified positive markers of mesothelioma and have potential to be included in future immunohistochemical marker panels for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma.

In plain English

This laboratory study from Hiroshima University, Japan, looked for new tissue-staining markers to help pathologists tell epithelioid mesothelioma apart from pulmonary adenocarcinoma, a lung cancer that can look similar under the microscope. It did not study asbestos exposure. The authors first compared gene activity in archived tumor tissue from 6 epithelioid mesotheliomas and 6 pulmonary adenocarcinomas. Two genes, DAB2 and Intelectin-1, were more active in the mesotheliomas. Both proteins were also found in all 5 mesothelioma cell lines tested. The authors then stained tissue from 75 epithelioid mesotheliomas and 67 pulmonary adenocarcinomas. DAB2 was positive in 60 of 75 mesotheliomas (80.0%) and 2 of 67 adenocarcinomas (3.0%). Intelectin-1 was positive in 57 of 75 mesotheliomas (76.0%) and in none of the adenocarcinomas. The authors concluded that these are new positive markers of epithelioid mesothelioma. They noted three limits: only 6 cases of each tumor went into the gene analysis, DAB2 also stains certain immune cells in lung tissue, and other institutes need to check the staining results.

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 marker study. Gene expression microarray analysis of archived tumor tissue, checked by RT-PCR and by Western blotting of cell lines, followed by an immunohistochemical (tissue staining) comparison of two tumor types
• Who was studied: Archived cases from the Department of Pathology, Hiroshima University, Japan. 75 patients with epithelioid mesothelioma (biopsy, surgery or autopsy, 2000 to 2016) and 67 pulmonary adenocarcinoma cases (surgery, 2005 to 2016). 6 cases of each were used for gene expression analysis. 5 commercially available mesothelioma cell lines were used for Western blotting.
• Exposure: Not studied. The article compared expression of tissue markers (DAB2, Intelectin-1, calretinin, D2-40, WT1) between tumor types and did not assess asbestos or any other exposure.
• Main results:
  • In the 6 versus 6 gene expression comparison, 902 statistically significant transcripts differed more than 1.3-fold between epithelioid mesothelioma and pulmonary adenocarcinoma. Of 426 protein-coding transcripts, 197 were higher in mesothelioma, including DAB2 and Intelectin-1.
  • Western blotting showed DAB2 and Intelectin-1 protein in all 5 mesothelioma cell lines
  • DAB2 staining was positive in 60 of 75 epithelioid mesotheliomas (80.0%) and 2 of 67 pulmonary adenocarcinomas (3.0%)
  • Intelectin-1 staining was positive in 57 of 75 epithelioid mesotheliomas (76.0%) and none of 67 pulmonary adenocarcinomas
  • For distinguishing epithelioid mesothelioma from pulmonary adenocarcinoma, sensitivity and specificity were 76.0% and 100% for Intelectin-1 and 80.0% and 97.0% for DAB2. For comparison, calretinin was 98.7% and 74.6%, D2-40 was 94.7% and 89.6%, and WT1 was 82.7% and 100%.
• The authors' conclusion: The authors concluded that they had identified DAB2 and Intelectin-1 as two novel positive markers of epithelioid mesothelioma that are useful for differentiating it from pulmonary adenocarcinoma by immunohistochemistry, and that other institutes should further validate them.
• Limitations the authors state:
  • Gene expression analysis included only 6 epithelioid mesotheliomas and 6 pulmonary adenocarcinomas. The authors stated that a larger number would make the findings more credible.
  • DAB2 also stains inflammatory cells, mainly macrophages, in pulmonary adenocarcinoma tissue, so results need careful interpretation
  • The functional roles of DAB2 and Intelectin-1 in epithelioid mesothelioma were not analyzed

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: Epithelioid, Mesothelioma, Adenocarcinoma, Malignant Mesothelioma, Differential Diagnosis.

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• Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells — K. Washimi, T. Yokose, et al. (2012)
• E-cadherin, E-selectin and vascular cell adhesion molecule: immunohistochemical markers for differentiation between mesothelioma and metastatic pulmonary adenocarcinoma? — A.M. Müller, A. Weichert, et al. (2002)
• MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma — V.J. Amatya, K. Kushitani, et al. (2017)
• Glypican-1 immunohistochemistry is a novel marker to differentiate epithelioid mesothelioma from lung adenocarcinoma — V.J. Amatya, K. Kushitani, et al. (2018)

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