The use of insulin like-growth factor II messenger RNA binding protein-3 in diagnostic pathology

Our plain-English summary of The use of insulin like-growth factor II messenger RNA binding protein-3 in diagnostic pathology, by J.J. Findeis-Hosey, H. Xu (Human Pathology, 2011).

The study

• Authors: J.J. Findeis-Hosey, H. Xu
• Journal: Human Pathology
• Published: 2011;42(3):303-14
• Type of article: Review
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The histologic distinction between reactive processes and malignant neoplasms and between low-grade and high-grade tumors is not always straightforward and is sometimes extremely challenging. This is especially the case when the diagnostic material is a small biopsy specimen or a cytology specimen with scant cellularity. In addition, suboptimal processing and crush artifact may limit accurate diagnosis. A reliable diagnostic biomarker that preferentially highlights malignant processes and high-grade tumors would be very valuable in segregating these entities from reactive processes and low-grade lesions. Recent extensive studies have shown that an oncoprotein, insulin like-growth factor II messenger RNA binding protein-3, is not only a prognostic biomarker but also a diagnostic molecule. This review focuses on discussing the value of insulin like-growth factor II messenger RNA binding protein-3 in diagnostic pathology, with a focus on utilization of insulin like-growth factor II messenger RNA binding protein-3 in the discrimination of benign effusions from malignant effusions, malignant mesothelioma from mesothelial hyperplasia, carcinoids from high-grade neuroendocrine carcinomas, low-grade dysplasia from high-grade dysplasia, hepatocellular carcinoma from hepatic adenoma, cholangiocarcinoma and metastatic pancreatic ductal carcinoma from benign bile duct lesions, melanoma from nevi, and follicular thyroid carcinoma from follicular adenoma of the thyroid, as well as examining insulin like-growth factor II messenger RNA binding protein-3 expression in lymphomas of germinal center origin.

Copyright © 2011 Elsevier Inc. All rights reserved.

In plain English

This was a review article, not a new study. The authors summarized published research on IMP3, a protein found in many cancers, and its use in telling malignant from benign or low-grade tissue under the microscope. The article does not discuss asbestos or any exposure. For mesothelioma, the review reported other studies' findings. In one fluid-sample study, 91% of malignant mesothelioma cases stained positive for IMP3. In another, 5.1% of reactive (non-cancerous) mesothelial cell samples were positive, compared with 72.6% of malignant effusions and 36.4% of malignant mesothelioma effusions. In tissue, an earlier study found IMP3 in 72.7% of malignant pleural mesotheliomas and none in normal mesothelial lining cells. The authors' own group reported moderate to strong staining in 64% of malignant pleural mesotheliomas, no staining in simple mesothelial hyperplasia, and variable staining in all 3 atypical hyperplasia cases. The review also covered esophageal, pancreatic, biliary, liver, skin, thyroid and lymphoid lesions. The authors concluded that, in multiple organ systems, IMP3 has been shown to be expressed in high-grade dysplasia and invasive lesions but typically not in low-grade dysplasia and benign lesions.

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: Narrative review of published studies on IMP3 as a diagnostic marker in pathology
• Who was studied: Published literature on IMP3 expression in human tumors and benign lesions across many organ systems, including effusion (body fluid) cytology and pleural mesothelioma specimens; no new patients were studied
• Main results:
  • In a reviewed study of serous fluid cytology (Hanley et al), IMP3 staining was positive in 91% of malignant mesothelioma cases and in 78% of malignant effusions whose primary tumor was IMP3 positive
  • In a reviewed effusion study (Ikeda et al), IMP3 was positive in 5.1% of reactive mesothelial cell cases, compared with 72.6% of malignant effusions and 36.4% of malignant mesothelioma effusions
  • In that same effusion study (Ikeda et al), the overall specificity for diagnosing malignancy was 94.9% and the sensitivity was 72.6%
  • In a reviewed tissue study (Sojka et al), IMP3 was positive in 72.7% of malignant pleural mesotheliomas, with no staining in normal mesothelial lining cells
  • In the authors' group's earlier study of surgical specimens, moderate to strong IMP3 staining was found in 64% of malignant pleural mesotheliomas
  • In the same earlier study by the authors' group, all simple mesothelial hyperplasia cases were negative for IMP3, and all 3 atypical mesothelial hyperplasia cases were variably positive
  • In a reviewed esophageal study (Lu et al), 94% of high-grade dysplasia cases were IMP3 positive, compared with 14% of low-grade dysplasia cases
• The authors' conclusion: The authors concluded that, across multiple organ systems, IMP3 has been shown to be expressed in high-grade dysplasia and invasive lesions but typically not in low-grade dysplasia and benign lesions
• Limitations the authors state:
  • The authors stated that how IMP3 works has not been fully worked out
  • The authors noted that the reviewed studies disagree on how IMP3 relates to prognosis in ovarian tumors

Topics

Medical terms in this study, explained in our Lexicon: Pathology, Neoplasm, Biopsy, Cytology, Biomarker, Malignant Mesothelioma, Reactive Mesothelial Hyperplasia, Carcinoma.

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• Practical utility of insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1, and epithelial membrane antigen for distinguishing malignant mesotheliomas from benign mesothelial proliferations — S. Chang, M.H. Oh, et al. (2014)
• Insulin-Like Growth Factor 2 mRNA Binding Protein 3 Promotes Cell Proliferation of Malignant Mesothelioma Cells by Downregulating p27Kip1 — I. Endo, V.J. Amatya, et al. (2021)
• Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages — P.W. Noble, F.R. Lake, et al. (1993)
• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression — A.W. Langerak, K.A. Williamson, et al. (1995)

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