Utility of a Highly Specific and Sensitive Podoplanin/D2-40, Calretinin, Thyroid Transcription Factor-1, and Carcinoembryonic Antigen/CD66e Immunohistochemical Panel in Differentiating Malignant Pleural Mesothelioma from Metastatic Adenocarcinoma: An Egyptian Experience

Our plain-English summary of Utility of a Highly Specific and Sensitive Podoplanin/D2-40, Calretinin, Thyroid Transcription Factor-1, and Carcinoembryonic Antigen/CD66e Immunohistochemical Panel in Differentiating Malignant Pleural Mesothelioma from Metastatic Adenocarcinoma: An Egyptian Experience, by R.A. Khairy, E. Khaled, S.E. Sheikh, et al (Journal of Microscopy and Ultrastructure, 2024).

The study

• Authors: R.A. Khairy, E. Khaled, S.E. Sheikh, A. Abdlaziz, S.E. Khalifa
• Journal: Journal of Microscopy and Ultrastructure
• Published: 2024;12(3):120-125
• Read it: PubMed · Publisher · Free full text

Abstract

Background And Objective: Considering plentiful immunohistochemical (IHC) antibodies, a selection of highly sensitive and specific targeted panels is necessary to differentiate malignant pleural mesothelioma (MPM) from metastatic adenocarcinoma. We aimed to examine the sensitivity and specificity of four markers (podoplanin [PDPN]/D2-40, calretinin, thyroid transcription factor-1 [TTF-1], and carcinoembryonic antigen [CEA]/CD66e) as an initial IHC panel of Egyptian patients with malignant pleural biopsies.

Materials And Methods: Forty Egyptian malignant pleural biopsies with histomorphological features of mesothelioma versus adenocarcinoma were immunohistochemically stained by PDPN/D2-40, calretinin, TTF-1, and CEA/CD66e.

Results: PDPN/D2-40 and calretinin were positive in 27/27, 100% of mesothelioma cases with 100% sensitivity, 96.4% specificity for PDPN/D2-40, and 100% sensitivity and specificity for calretinin. Membranous PDPN/D2-40 expression was strong in 14 cases (53.85%), moderate in eight cases (30.77%), and weak in four cases (15.38%), while pure cytoplasmic staining was reported in one case. Calretinin was predominantly nuclear in all mesothelioma cases. TTF1 and CEA/CD66e were negative in all mesothelioma cases. In adenocarcinomas, PDPN/D2-40 was only expressed as weak cytoplasmic staining in 1/13 cases, while calretinin was negative in all 13 cases. Nuclear TTF1 and cytoplasmic CEA/CD66e immunostaining positivity were reported in all adenocarcinoma cases (13/13) with 100% sensitivity and specificity for both markers.

Conclusion: The combination of PDPN/D2-40, calretinin together with CEA/CD66e, and TTF1 may be highly valuable in differentiating MPM from metastatic adenocarcinoma.

Copyright: © 2022 Journal of Microscopy and Ultrastructure.

In plain English

This study from the Department of Pathology at Cairo University, Egypt, tested whether four laboratory stains could tell malignant pleural mesothelioma apart from metastatic adenocarcinoma, which is cancer that has spread to the pleura from elsewhere. The authors stained 40 malignant pleural biopsies whose appearance under the microscope suggested either disease. Based on the panel results, 27 were classed as mesothelioma (25 epithelioid, one sarcomatoid, one biphasic) and 13 as metastatic adenocarcinoma. Podoplanin/D2-40 and calretinin stained all 27 mesotheliomas. Podoplanin also weakly stained 1 of the 13 adenocarcinomas, while calretinin stained none. TTF-1 and CEA/CD66e stained all 13 adenocarcinomas and none of the mesotheliomas. The authors reported 100% sensitivity for each marker, and specificity of 96.4% for podoplanin and 100% for the other three. The authors concluded that this combination might be very useful in distinguishing mesothelioma from metastatic adenocarcinoma. The article did not report asbestos exposure and did not state limitations. Some of its podoplanin figures are internally inconsistent.

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 study of immunohistochemical staining on pleural biopsies, reporting sensitivity, specificity and predictive values
• Who was studied: 40 malignant pleural biopsies from Egyptian patients (Kasr Alainy, Cairo University), with microscopic features suggesting mesothelioma versus metastatic adenocarcinoma. Based on the panel, 27 were mesothelioma (25 epithelioid, 1 sarcomatoid, 1 biphasic) and 13 were metastatic adenocarcinoma. Collection dates are not given; ethics approval was in March 2019.
• Exposure: Not an asbestos exposure study. No asbestos or other exposure history was reported. The study evaluated four stains: podoplanin/D2-40, calretinin, TTF-1 and CEA/CD66e.
• Main results:
  • Of the 40 biopsies, 27 were confirmed as malignant pleural mesothelioma and 13 as metastatic adenocarcinoma, based on the panel results.
  • Mesothelioma patients: most were 50 years or older (19/27, 70.4%) and most were male (20/27, 74.1%).
  • Podoplanin/D2-40 was positive in 27/27 (100%) of mesotheliomas, with reported sensitivity 100% and specificity 96.4%.
  • Podoplanin/D2-40 was positive in 1 of 13 adenocarcinomas (7.7%), as cytoplasmic staining in fewer than 25% of tumor cells.
  • Calretinin was positive in all 27 mesotheliomas and negative in all 13 adenocarcinomas (0/13), with 100% sensitivity and 100% specificity.
  • TTF-1 was positive (nuclear) in all 13 adenocarcinomas and in none of the 27 mesotheliomas.
  • CEA/CD66e was positive in all 13 adenocarcinomas (13/13) and negative in all 27 mesotheliomas.
  • In the mesotheliomas, 26/27 (96.3%) showed membranous podoplanin/D2-40 staining. Its intensity was strong in 14 (53.8%), moderate in 8 (30.8%) and weak in 4 (15.4%).
• The authors' conclusion: The authors concluded that membranous podoplanin/D2-40 staining with nuclear calretinin, combined with cytoplasmic CEA/CD66e and nuclear TTF-1, might be very useful in distinguishing mesothelioma from metastatic adenocarcinoma. They also encouraged further studies of podoplanin/D2-40 as a possible prognostic marker and treatment target.

Topics

Medical terms in this study, explained in our Lexicon: Podoplanin (D2-40), Calretinin, Thyroid Transcription Factor-1 (TTF-1), Carcinoembryonic Antigen (CEA), Pleural Mesothelioma, Adenocarcinoma, Mesothelioma.

Related studies

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