Podoplanin is a useful marker for identifying mesothelioma in malignant effusions

Our plain-English summary of Podoplanin is a useful marker for identifying mesothelioma in malignant effusions, by A. Hanna, Y. Pang, C.W. Bedrossian, et al (Diagnostic Cytopathology, 2010).

The study

• Authors: A. Hanna, Y. Pang, C.W. Bedrossian, A. Dejmek, C.W. Michael
• Journal: Diagnostic Cytopathology
• Published: 2010;38(4):264-9
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The diagnosis of malignant mesothelioma in serosal effusions continues to be a major challenge because some of its cytomorphological features closely resemble adenocarcinomas. Immunohistochemistry is a valuable tool in the differentiation of epithelioid mesothelioma from metastatic adenocarcinomas. However, no single antibody has demonstrated absolute sensitivity or specificity. In this study, we evaluated the value of immunostaining pattern for podoplanin to differentiate mesothelioma from adenocarcinomas of various origins.Cell blocks from previously collected paraffin-embedded cell blocks of 86 effusions (18 mesothelioma, 35 reactive mesothelium, 9 breast adenocarcinoma, 14 ovarian adenocarcinoma, and 10 lung adenocarcinoma) were retrieved from the file of the Department of Pathology at University of Michigan and Lund University in Sweden and were used for the study. Slides prepared from the cell blocks were stained for podoplanin. The percentage of immunostained cells was recorded as follows: 1+ (5-25%), 2+ (26-50%), and 3+ (>50%). A stain result involving <5% of cells was considered negative. The intensity of positive results was evaluated as strong, moderate, or weak.Podoplanin is expressed in 94% of malignant mesothelioma cases (17/18), 97% (30/31) of cases of reactive mesothelial, 0% of lung adenocarcinoma cases (0/9), 0% of breast adenocarcinoma (0/9), and 7% of ovarian adenocarcinoma (1/14). All positive cases of malignant mesothelioma and reactive mesothelium showed strong membranous reactivity to podoplanin. The one positive case of ovarian adenocarcinoma showed a weak membranous podoplanin immunostaining.On the basis of our results and published data, we believe that membranous podoplanin immunoreactivity, in conjunction with calretinin, would be more specific than CK5/6 and WT-1 in differentiating epithelioid malignant mesothelioma from adenocarcinoma of the lung, breast, and ovary.

Copyright 2009 Wiley-Liss, Inc.

In plain English

This laboratory study tested whether a stain for the protein podoplanin can help pathologists tell mesothelioma apart from other cancers in fluid collected from around the lungs (effusions). The authors stained archived cell samples from 86 effusions from the University of Michigan and Lund University in Sweden: 18 epithelioid mesothelioma, 35 reactive (non-cancerous) mesothelium, and adenocarcinomas of the breast (9), ovary (14) and lung (10). Five samples were excluded because they had too few cells. A membrane staining pattern appeared in 17 of 18 mesotheliomas (94%) and 30 of 31 reactive mesothelium samples (97%). It appeared in 1 of 32 adenocarcinomas (3%), a weakly stained ovarian case. Reactive and malignant mesothelial cells stained alike, so the authors stated that podoplanin cannot tell them apart. Based on their results and published data, the authors concluded that podoplanin together with calretinin would be more specific than the markers CK5/6 and WT-1 for separating epithelioid mesothelioma from these adenocarcinomas. Calretinin, CK5/6 and WT-1 were not tested here. The study did not examine asbestos exposure. Some figures differ between sections of the article.

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: immunohistochemical staining for podoplanin on archived, previously collected cell blocks from effusions
• Who was studied: 86 effusion cell-block cases from the University of Michigan (Ann Arbor) and Lund University, Sweden: 18 epithelioid mesothelioma, 35 reactive mesothelium, 9 breast ductal adenocarcinoma, 14 ovarian serous adenocarcinoma and 10 lung adenocarcinoma. Four reactive mesothelium cases and one lung adenocarcinoma case were excluded for very low cellularity, leaving 31 reactive and 9 lung cases. Collection dates are not given.
• Exposure: No asbestos exposure was studied or reported. The test examined was a mouse monoclonal antibody stain for podoplanin, used at 1:200 dilution.
• Main results:
  • In the malignant mesothelioma cases, 17 of 18 (94%) showed podoplanin staining with a membranous pattern in more than 50% of cells
  • In the mesothelioma cases, membranous staining intensity was strong in 8 (44%), moderate in 5 (28%) and weak in 4 (22%). One further mesothelioma case (6%) showed moderate cytoplasmic staining.
  • All 31 reactive mesothelium cases stained for podoplanin: 30 of 31 (97%) with a membranous pattern and one with a cytoplasmic pattern
  • None of the lung (0/9) or breast (0/9) adenocarcinoma cases showed membranous podoplanin staining
  • Weak, diffuse cytoplasmic staining was reported in 1/9 (11%) lung adenocarcinoma and 2/9 (22%) breast carcinoma cases, according to the Discussion and Table II. The Results text instead gives 2/9 for lung.
  • One of 14 ovarian adenocarcinoma cases (7%) showed weak membranous staining in less than 25% of cells
  • Overall, podoplanin stained 97% of reactive mesothelium cases, 94% of malignant mesothelioma cases and 3% of all adenocarcinoma cases (1/32)
  • Staining intensity in reactive mesothelium was comparable to that in malignant mesothelioma, so the authors stated that podoplanin does not distinguish malignant from reactive mesothelial cells
• The authors' conclusion: The authors concluded, on the basis of their results and published data, that membranous podoplanin staining together with calretinin would be more specific than CK5/6 and WT-1 in differentiating epithelioid malignant mesothelioma from adenocarcinoma of the lung, breast and ovary. They also stated that none of these markers is useful for telling reactive mesothelial cells from epithelioid malignant mesothelioma. Calretinin, CK5/6 and WT-1 were not stained in this study.
• Limitations the authors state:
  • The authors stated that more ovarian adenocarcinoma cases need to be examined to determine the accurate percentage showing membranous podoplanin staining
  • The authors stated that the weak cytoplasmic staining seen in a few lung and breast adenocarcinomas needs further investigation of its significance and reproducibility

Topics

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

Medical terms in this study, explained in our Lexicon: Podoplanin (D2-40), Mesothelioma, Malignant Mesothelioma, Adenocarcinoma, Immunohistochemistry, Epithelioid, Cell Block, Mesothelium.

Related studies

• Value of podoplanin as an immunohistochemical marker in tumor diagnosis: a review and update — N.G. Ordóñez (2014)
• Expression of podoplanin and calretinin in meningioma: an immunohistochemical study — M. Shintaku, T. Honda, et al. (2010)
• Mediastinal and pleuropulmonary myeloid sarcoma with HBME1 and podoplanin expression. A diagnostic pitfall — D. Suárez-Vilela, F.M. Izquierdo (2020)
• IMP3/L523S, a novel immunocytochemical marker that distinguishes benign and malignant cells: the expression profiles of IMP3/L523S in effusion cytology — K. Ikeda, G. Tate, et al. (2010)
• EZH2, a unique marker of malignancy in effusion cytology — H. Jiang, R. Gupta, et al. (2014)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)

Browse more research in Diagnostic Cytopathology, or return to medical research.