The differential expression of N-cadherin and E-cadherin distinguishes pleural mesotheliomas from lung adenocarcinomas

Our plain-English summary of The differential expression of N-cadherin and E-cadherin distinguishes pleural mesotheliomas from lung adenocarcinomas, by A. Peralta Soler, K.A. Knudsen, M.C. Jaurand, et al (Human Pathology, 1995).

The study

• Authors: A. Peralta Soler, K.A. Knudsen, M.C. Jaurand, K.R. Johnson, M.J. Wheelock, A.J. Klein-Szanto, H. Salazar
• Journal: Human Pathology
• Published: 1995;26(12):1363-9
• Cited by: 83 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesotheliomas are highly aggressive tumors that develop most frequently in the pleura of patients chronically exposed to asbestos. The distinction between malignant mesotheliomas and tumors of epithelial origin, particularly peripheral lung adenocarcinoma, can be difficult despite the use of immunocytochemical markers and other diagnostic tools. During embryonic development the cadherin cell-cell adhesion molecules participate in the segregation of cells into different tissues. As a result of complex mechanisms of tissue selectivity, N-cadherin is expressed by the developing pleural mesothelial cells and E-cadherin is expressed by the epithelial cells of the lung. Thus, we postulated that N-cadherin could be used as a marker of mesothelial cells and mesothelial tumors, in contrast to adenocarcinomas of the lung that are tumors of epithelial origin. We studied the expression of N-cadherin, E-cadherin and two cadherin-associated proteins, alpha-catenin and beta-catenin, in 19 pleural mesotheliomas, 16 lung adenocarcinomas and in 2 mesothelioma cell lines using specific monoclonal antibodies and immunohistochemical methods. Our results show that all mesotheliomas express high levels of N-cadherin, regardless of their histological type, in contrast to lung adenocarcinomas which expressed E-cadherin but no N-cadherin. The cadherin-associated proteins, alpha-catenin and beta-catenin, were present in both mesotheliomas and adenocarcinomas. Our results show that pleural mesotheliomas can be distinguished from lung adenocarcinomas based on the differential expression of N-cadherin and E-cadherin, using specific monoclonal antibodies and immunocytochemistry.

In plain English

This laboratory study tested whether two cell-surface proteins, N-cadherin and E-cadherin, could help tell pleural mesothelioma apart from lung adenocarcinoma. The authors stained frozen tumor tissue from 19 pleural mesotheliomas and 16 lung adenocarcinomas, plus two cell lines grown from epithelioid mesotheliomas. They used antibodies against N-cadherin, E-cadherin and two related proteins, alpha-catenin and beta-catenin. The mesotheliomas included epithelioid, biphasic and sarcomatous types, and all of them showed abundant N-cadherin. Eight mesotheliomas also showed weak, mostly cytoplasmic E-cadherin staining. All adenocarcinomas showed E-cadherin. N-cadherin was absent in 13 adenocarcinomas and weakly present in a small share of cells in 3. The catenins appeared in both tumor types. Both cell lines showed intense N-cadherin at the cell membrane. The authors concluded that N-cadherin and E-cadherin are diagnostic markers for distinguishing these tumors and that both should be analyzed. They noted that only frozen tissue was used. The study did not examine asbestos exposure, and the article gives no exposure information for the patients.

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 pathology study: immunohistochemistry and immunofluorescence staining of frozen tumor tissue and cultured mesothelioma cell lines, comparing two tumor types
• Who was studied: Frozen tumor tissue from 19 pleural mesotheliomas (11 from the University of Pennsylvania Hospital, 7 from the Fox Chase Cancer Center tumor bank, 1 from The Lankenau Hospital, all in Pennsylvania) and 16 lung adenocarcinomas (Fox Chase Cancer Center tumor bank), plus 2 cell lines from human epithelioid mesotheliomas (one well differentiated, one poorly differentiated) obtained from Creteil, France. The mesotheliomas were epithelioid, biphasic or sarcomatous.
• Exposure: Not studied. The study examined protein markers in tumor tissue; the article reports no asbestos or other exposure information for the patients.
• Main results:
  • All 19 pleural mesotheliomas, of every histological type, expressed abundant N-cadherin.
  • In 8 of the mesotheliomas, weak and mostly cytoplasmic E-cadherin staining was also seen.
  • All 16 lung adenocarcinomas expressed E-cadherin.
  • N-cadherin was absent in 13 of the 16 lung adenocarcinomas. In the other 3 it was weakly expressed in the cytoplasm of a small percentage of tumor cells.
  • Alpha-catenin and beta-catenin were found in both mesotheliomas and lung adenocarcinomas.
  • In the lung adenocarcinomas, the intensity of E-cadherin staining did not correlate with histological grade. The authors did not show these data.
  • Both mesothelioma cell lines (well and poorly differentiated) showed intense N-cadherin expression at the plasma membrane. E-cadherin staining in the cell lines was weak and intracytoplasmic.
• The authors' conclusion: The authors concluded that N-cadherin and E-cadherin are diagnostic markers for distinguishing pleural mesotheliomas from lung adenocarcinomas: high N-cadherin marks mesotheliomas and high E-cadherin marks lung adenocarcinomas.
• Limitations the authors state:
  • Only frozen tissue was used. Work to adapt the antibodies to routinely processed formalin-fixed, paraffin-embedded tissue was still under way.
  • N-cadherin is also present in non-tumor stromal tissue. This limited the use of Western immunoblots to detect N-cadherin in tumor tissue samples.
  • Some mesotheliomas showed low levels of E-cadherin and some adenocarcinomas showed low levels of N-cadherin. The authors therefore stated that both cadherins should be 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: Pleural Mesothelioma, Lung Adenocarcinoma, Malignant Mesothelioma, Pleura, Mesothelial Cells, Adenocarcinoma, Mesothelioma, Monoclonal.

Related studies

• Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues — A.C. Han, A. Peralta-Soler, et al. (1997)
• E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma — M.P. Leers, M.M. Aarts, et al. (1998)
• 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)
• E-cadherin in mesothelioma — M. Jeffers (1996)
• Expression of E-cadherin in bone and soft tissue sarcomas: a possible role in epithelial differentiation — H. Sato, T. Hasegawa, et al. (1999)
• E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells — T. Kato, T. Sato, et al. (2017)

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