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Cadherins, catenins and APC in pleural malignant mesothelioma

Cadherins, catenins and APC in pleural malignant mesothelioma
Cadherins, catenins and APC in pleural malignant mesothelioma
Malignant mesothelioma is an aggressive disease of the pleura, and less commonly the peritoneum, with a very poor prognosis. The present study has examined the expression of cell adhesion molecules including cadherins, catenins, and APC in order to determine whether abnormal expression of components of the Wnt signalling pathway contribute to the variable phenotype of malignant mesothelioma. Sixty-three malignant mesotheliomas and nine cases of reactive mesothelial hyperplasia were analysed by immunohistochemistry for E-cadherin, N-cadherin, ?-catenin, ?-catenin, and the C- and N-terminals of APC. In addition, DNA was extracted from formalin-fixed, paraffin wax blocks, and a 226 bp fragment of exon 3 of the -catenin gene was amplified, sequenced, and screened for activating mutations in the glycogen synthase kinase 3? (GSK-3?) phosphorylation targets. E-cadherin expression was detected in 48% of the epithelioid mesotheliomas but was observed in only 7% of sarcomatoid mesotheliomas. N-cadherin, ?-catenin, ?-catenin, and the C- and N-terminals of APC did not show differential expression between the mesothelioma phenotypes. Abnormal nuclear localization of -catenin was demonstrated in 19% of mesotheliomas.
Mutations of ?-catenin phosphorylation sites were not detected in any of the 62 mesotheliomas examined. Positive staining for the N-terminal of APC was seen in all of the cases of reactive mesothelial hyperplasia, as well as in all the mesotheliomas. Staining for the C-terminal of APC was negative in 23% mesotheliomas, despite being present in all the cases of reactive hyperplasia. The present study provides the first evidence that ?-catenin accumulates in the nucleus in malignant mesotheliomas. In addition, APC expression was altered in some mesotheliomas, suggesting that a truncated APC gene product may contribute to abnormal Wnt signalling and dysregulation of cell proliferation in malignant mesothelioma.
malignant mesothelioma, wnt signalling, cadherins, ?-catenin, adenomatous polyposis coli
1096-9896
355-362
Abutaily, A.S.
7682274e-a978-4c04-ba81-732f302c6340
Collins, J.E.
be0e66f1-3036-47fa-9d7e-914c48710ba4
Roche, W.R.
a5135b2d-cab5-481b-887a-78611fa00bff
Abutaily, A.S.
7682274e-a978-4c04-ba81-732f302c6340
Collins, J.E.
be0e66f1-3036-47fa-9d7e-914c48710ba4
Roche, W.R.
a5135b2d-cab5-481b-887a-78611fa00bff

Abutaily, A.S., Collins, J.E. and Roche, W.R. (2003) Cadherins, catenins and APC in pleural malignant mesothelioma. The Journal of Pathology, 201 (3), 355-362. (doi:10.1002/path.1458). (PMID:14595746)

Record type: Article

Abstract

Malignant mesothelioma is an aggressive disease of the pleura, and less commonly the peritoneum, with a very poor prognosis. The present study has examined the expression of cell adhesion molecules including cadherins, catenins, and APC in order to determine whether abnormal expression of components of the Wnt signalling pathway contribute to the variable phenotype of malignant mesothelioma. Sixty-three malignant mesotheliomas and nine cases of reactive mesothelial hyperplasia were analysed by immunohistochemistry for E-cadherin, N-cadherin, ?-catenin, ?-catenin, and the C- and N-terminals of APC. In addition, DNA was extracted from formalin-fixed, paraffin wax blocks, and a 226 bp fragment of exon 3 of the -catenin gene was amplified, sequenced, and screened for activating mutations in the glycogen synthase kinase 3? (GSK-3?) phosphorylation targets. E-cadherin expression was detected in 48% of the epithelioid mesotheliomas but was observed in only 7% of sarcomatoid mesotheliomas. N-cadherin, ?-catenin, ?-catenin, and the C- and N-terminals of APC did not show differential expression between the mesothelioma phenotypes. Abnormal nuclear localization of -catenin was demonstrated in 19% of mesotheliomas.
Mutations of ?-catenin phosphorylation sites were not detected in any of the 62 mesotheliomas examined. Positive staining for the N-terminal of APC was seen in all of the cases of reactive mesothelial hyperplasia, as well as in all the mesotheliomas. Staining for the C-terminal of APC was negative in 23% mesotheliomas, despite being present in all the cases of reactive hyperplasia. The present study provides the first evidence that ?-catenin accumulates in the nucleus in malignant mesotheliomas. In addition, APC expression was altered in some mesotheliomas, suggesting that a truncated APC gene product may contribute to abnormal Wnt signalling and dysregulation of cell proliferation in malignant mesothelioma.

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More information

Published date: November 2003
Keywords: malignant mesothelioma, wnt signalling, cadherins, ?-catenin, adenomatous polyposis coli
Organisations: Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 179889
URI: http://eprints.soton.ac.uk/id/eprint/179889
ISSN: 1096-9896
PURE UUID: 19e62a9e-68e1-4f3e-985f-236bd66e571a

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Date deposited: 06 Apr 2011 09:05
Last modified: 22 Jul 2022 17:37

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Contributors

Author: A.S. Abutaily
Author: J.E. Collins
Author: W.R. Roche

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