A novel biotinylated probe specific for hyaluronate. Its diagnostic value in diffuse malignant mesothelioma

Our plain-English summary of A novel biotinylated probe specific for hyaluronate. Its diagnostic value in diffuse malignant mesothelioma, by N. Azumi, C.B. Underhill, E. Kagan, et al (The American Journal of Surgical Pathology, 1992).

The study

• Authors: N. Azumi, C.B. Underhill, E. Kagan, K. Sheibani
• Journal: The American Journal of Surgical Pathology
• Published: 1992;16(2):116-21
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Diffuse malignant mesotheliomas are known to secrete a large amount of hyaluronate, whereas adenocarcinomas produce predominantly neutral mucins. In the present study, we assessed the diagnostic usefulness of a new, highly specific and sensitive hyaluronate binding probe to discriminate between mesotheliomas and adenocarcinomas. We studied 33 mesotheliomas and 37 adenocarcinomas in order to establish specific diagnostic criteria for using the hyaluronate binding probe. Of the adenocarcinomas, only three showed significant positive staining for hyaluronate (8%). By contrast, all the mesotheliomas exhibited positive staining for hyaluronate. Furthermore, the staining reaction was classed as moderate or greater in 26 mesotheliomas (79%), thus suggesting the utility of this probe in the differential diagnosis of malignant mesothelioma versus adenocarcinoma. We conclude that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. The hyaluronate binding probe should therefore be considered an important adjunct to be used in combination with electron microscopy and immunohistochemistry in the histologic diagnosis of diffuse malignant mesothelioma.

In plain English

This laboratory study tested whether a new probe that binds hyaluronate could help distinguish diffuse malignant mesothelioma from adenocarcinoma in tissue samples. The authors noted that mesotheliomas are known to secrete large amounts of hyaluronate. They stained 33 mesotheliomas (32 pleural, one peritoneal) and 37 adenocarcinomas (30 involving the lung, seven of gastrointestinal origin). Two pathologists scored the slides without knowing the diagnosis. Weak staining counted as negative. All 33 mesotheliomas showed at least focal moderate to strong staining, and 26 (79%) showed moderate to strong staining in 30% or more of tumor cells. Three of the 37 adenocarcinomas (8%) reached that higher level. With that higher level as the cutoff, the test identified mesothelioma with 79% sensitivity and 92% specificity. With at least focal moderate to strong staining as the cutoff, the figures were 100% and 68%. The authors concluded that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. They noted three limits. They did not specifically look for adenocarcinomas that mimic pleural mesothelioma. Few non-lung adenocarcinomas were studied. The appearance of the stained slides gave some hint of the diagnosis.

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 pathology study comparing staining of tumor tissue samples, with slides scored blind to diagnosis
• Who was studied: Tissue samples from 33 diffuse malignant mesotheliomas (32 pleural, one peritoneal) and 37 adenocarcinomas (30 involving the lung, seven of gastrointestinal origin). Five mesotheliomas came from Georgetown University Medical Center. The other mesotheliomas and all the adenocarcinomas came from City of Hope National Medical Center. The mesotheliomas selected had negative CEA and Leu-M1 immunoreactivity. The article does not give dates.
• Main results:
  • Scoring scale: negative or weak staining was scored 0. Focal moderate to strong staining in less than 30% of tumor cells was scored 1. Moderate to strong staining in 30% to 60% of tumor cells was scored 2, and in more than 60% was scored 3.
  • All 33 mesotheliomas scored 1 or greater, meaning at least focal moderate to strong membranous or cytoplasmic staining.
  • 26 of the 33 mesotheliomas (79%) were classed as moderate or greater. Table 3 counts these as a score of 2 to 3, which means moderate to strong staining in 30% or more of tumor cells.
  • Three of the 37 adenocarcinomas (8%) showed significant positive staining, a score of 2 or greater. The text also reports that 11 adenocarcinomas (30%) showed some positive staining.
  • With a score of 2 as the cutoff (moderate to strong cytoplasmic or membranous staining in 30% or more of tumor cells), sensitivity for mesothelioma was 79% and specificity was 92%.
  • With a score of 1 as the cutoff (at least focal moderate to strong staining; weak staining scored 0), sensitivity was 100% and specificity was 68%.
• The authors' conclusion: The authors concluded that strong cytoplasmic or membranous staining for hyaluronate is highly predictive of malignant mesothelioma. They said the probe should be considered an adjunct to electron microscopy and immunohistochemistry in diagnosing diffuse malignant mesothelioma.
• Limitations the authors state:
  • The authors did not specifically seek adenocarcinoma cases that mimic pleural mesothelioma.
  • Only a small number of non-lung adenocarcinomas were studied, so the authors said their impression about tumor site needs confirmation.
  • Although scoring was blinded, the appearance of the stained slides gave some indication of the diagnosis.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Adenocarcinoma, Mesothelioma, Differential Diagnosis, Immunohistochemistry.

Related studies

• Hyaluronate binding probe and CD44 in the differential diagnosis of malignant effusions: disappointing results in cytology material — A.C. Filie, A. Abati, et al. (1998)
• Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin — G. Ak, Y. Tada, et al. (2017)
• Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura — C. González-Lois, C. Ballestín, et al. (2001)
• 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)
• Combined hyaluronate-based films loaded with pemetrexed and cisplatin for the treatment of malignant pleural mesothelioma: Preliminary evaluation in an orthotopic tumor recurrence model — F. Sonvico, S. Barbieri, et al. (2018)
• Effect of hyaluronate on the electrophoretic migration of plasma proteins in pleural fluid — G. Lindstedt (1970)

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