Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients

Introduction. Familial adenomatous polyposis (FAP) patients have a germline mutation in the adenomatous polyposis coli (APC) gene. The APC protein interacts with beta-catenin, resulting in the activation of the Wnt signalling pathway. This results in alterations in cell proliferation and apoptosis....

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Main Authors: Jayson Wang, Nabil El-Masry, Ian Talbot, Ian Tomlinson, Malcolm R. Alison, Mona El-Bahrawy
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2013/107534
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author Jayson Wang
Nabil El-Masry
Ian Talbot
Ian Tomlinson
Malcolm R. Alison
Mona El-Bahrawy
author_facet Jayson Wang
Nabil El-Masry
Ian Talbot
Ian Tomlinson
Malcolm R. Alison
Mona El-Bahrawy
author_sort Jayson Wang
collection DOAJ
description Introduction. Familial adenomatous polyposis (FAP) patients have a germline mutation in the adenomatous polyposis coli (APC) gene. The APC protein interacts with beta-catenin, resulting in the activation of the Wnt signalling pathway. This results in alterations in cell proliferation and apoptosis. We investigated the expression of beta-catenin and related proliferation and apoptotic factors in FAP patients, exploring the expression along the adenoma-carcinoma sequence. Methods. The expression of beta-catenin, p53, bcl-2, cyclin-D1, caspase-3, CD10, and Ki-67 proteins was studied by immunohistochemistry in samples of colonic nonneoplastic mucosa (n=71), adenomas (n=152), and adenocarcinomas (n=19) from each of the16 FAP patients. Results. The expression of beta-catenin, caspase-3, cyclin-D1, and Ki-67 was increased in both adenomas and carcinomas in FAP patients, compared with normal mucosa. p53 and CD10 expression was only slightly increased in adenomas, but more frequently expressed in carcinomas. Bcl-2 expression was increased in adenomas, but decreased in carcinomas. Conclusion. This is the first study investigating collectively the expression of these molecules together in nonneoplastic mucosa, adenomas, and carcinomas from FAP patients. We find that beta-catenin and related proliferative and apoptotic factors (cyclin-D1, bcl-2, caspase-3, and Ki-67) are expressed early in the sequence, in adenomas. However, p53 and CD10 are often expressed later in the sequence, in carcinomas.
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spelling doaj-art-36942c1895fe446694a303fa5c8c08d42025-02-03T01:03:04ZengWileyGastroenterology Research and Practice1687-61211687-630X2013-01-01201310.1155/2013/107534107534Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis PatientsJayson Wang0Nabil El-Masry1Ian Talbot2Ian Tomlinson3Malcolm R. Alison4Mona El-Bahrawy5Department of Histopathology, Imperial College London, Hammersmith Hospital, DuCane Road, London W12 0HS, UKDepartment of Surgery, Faculty of Medicine, Alexandria University, Alexandria, EgyptDepartment of Histopathology, St. Mark’s Hospital, London HA1 3UJ, UKWellcome Trust Centre for Human Genetics, University of Oxford and NIHR Oxford Biomedical Research Centre, Oxford OX3 7BN, UKCentre for Tumour Biology, Barts Cancer Institute, Queen Mary, University of London, London EC1M 6BQ, UKDepartment of Histopathology, Imperial College London, Hammersmith Hospital, DuCane Road, London W12 0HS, UKIntroduction. Familial adenomatous polyposis (FAP) patients have a germline mutation in the adenomatous polyposis coli (APC) gene. The APC protein interacts with beta-catenin, resulting in the activation of the Wnt signalling pathway. This results in alterations in cell proliferation and apoptosis. We investigated the expression of beta-catenin and related proliferation and apoptotic factors in FAP patients, exploring the expression along the adenoma-carcinoma sequence. Methods. The expression of beta-catenin, p53, bcl-2, cyclin-D1, caspase-3, CD10, and Ki-67 proteins was studied by immunohistochemistry in samples of colonic nonneoplastic mucosa (n=71), adenomas (n=152), and adenocarcinomas (n=19) from each of the16 FAP patients. Results. The expression of beta-catenin, caspase-3, cyclin-D1, and Ki-67 was increased in both adenomas and carcinomas in FAP patients, compared with normal mucosa. p53 and CD10 expression was only slightly increased in adenomas, but more frequently expressed in carcinomas. Bcl-2 expression was increased in adenomas, but decreased in carcinomas. Conclusion. This is the first study investigating collectively the expression of these molecules together in nonneoplastic mucosa, adenomas, and carcinomas from FAP patients. We find that beta-catenin and related proliferative and apoptotic factors (cyclin-D1, bcl-2, caspase-3, and Ki-67) are expressed early in the sequence, in adenomas. However, p53 and CD10 are often expressed later in the sequence, in carcinomas.http://dx.doi.org/10.1155/2013/107534
spellingShingle Jayson Wang
Nabil El-Masry
Ian Talbot
Ian Tomlinson
Malcolm R. Alison
Mona El-Bahrawy
Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients
Gastroenterology Research and Practice
title Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients
title_full Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients
title_fullStr Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients
title_full_unstemmed Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients
title_short Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients
title_sort expression profiling of proliferation and apoptotic markers along the adenoma carcinoma sequence in familial adenomatous polyposis patients
url http://dx.doi.org/10.1155/2013/107534
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