BACKGROUND: Fundic gland polyps (FGPs) occur in both syndromic and sporadic form. Syndromic FGPs arise through mutations in the adenomatous polyposis coli (APC) gene, whereas sporadic FGPs are caused by beta-catenin gene mutations. Dysplasia in sporadic FGPs, found less often than in syndromic FGPs, was recently associated with APC rather than beta-catenin mutations. These data suggest different functional consequences of APC and beta-catenin mutations. To investigate this hypothesis, we examined proliferative activity, degree of apoptosis, beta-catenin expression and p53 expression in syndromic and sporadic FGPs. METHODS: Syndromic FGPs (n = 9) from familial adenomatous polyposis (FAP) patients and sporadic FGPs (n = 18) were studied. Proliferative activity, apoptotic cell death and expression of beta-catenin and p53 were examined by immunohistochemistry. In FGPs containing dysplasia, areas with and without dysplasia were compared. RESULTS: Syndromic and sporadic FGPs without dysplasia exhibited similar proliferative activity, degree of apoptosis, beta-catenin and p53 expression. Dysplasia was observed more often in syndromic (4/9) than in sporadic FGPs (1/18). Within FGPs containing dysplasia, dysplastic areas showed abnormal nuclear beta-catenin staining in 3/5 cases and higher rates of cell proliferation and apoptosis than non-dysplastic areas. Overexpression of p53 was not observed. CONCLUSION: The finding of similar rates of proliferation and apoptosis in syndromic and sporadic FGPs does not support the hypothesis that APC and beta-catenin gene mutations have different functional consequences in FGPs. The association of dysplasia with relatively high cell turnover rates and nuclear expression of beta-catenin indicates activation of the Wnt-APC-beta-catenin pathway in dysplasia. The finding of dysplasia in some but not all syndromic FGPs suggests the involvement of other genes in addition to the APC gene in the development of dysplasia in FGPs.
BACKGROUND:Fundic gland polyps (FGPs) occur in both syndromic and sporadic form. Syndromic FGPs arise through mutations in the adenomatous polyposis coli (APC) gene, whereas sporadic FGPs are caused by beta-catenin gene mutations. Dysplasia in sporadic FGPs, found less often than in syndromic FGPs, was recently associated with APC rather than beta-catenin mutations. These data suggest different functional consequences of APC and beta-catenin mutations. To investigate this hypothesis, we examined proliferative activity, degree of apoptosis, beta-catenin expression and p53 expression in syndromic and sporadic FGPs. METHODS: Syndromic FGPs (n = 9) from familial adenomatous polyposis (FAP) patients and sporadic FGPs (n = 18) were studied. Proliferative activity, apoptotic cell death and expression of beta-catenin and p53 were examined by immunohistochemistry. In FGPs containing dysplasia, areas with and without dysplasia were compared. RESULTS: Syndromic and sporadic FGPs without dysplasia exhibited similar proliferative activity, degree of apoptosis, beta-catenin and p53 expression. Dysplasia was observed more often in syndromic (4/9) than in sporadic FGPs (1/18). Within FGPs containing dysplasia, dysplastic areas showed abnormal nuclear beta-catenin staining in 3/5 cases and higher rates of cell proliferation and apoptosis than non-dysplastic areas. Overexpression of p53 was not observed. CONCLUSION: The finding of similar rates of proliferation and apoptosis in syndromic and sporadic FGPs does not support the hypothesis that APC and beta-catenin gene mutations have different functional consequences in FGPs. The association of dysplasia with relatively high cell turnover rates and nuclear expression of beta-catenin indicates activation of the Wnt-APC-beta-catenin pathway in dysplasia. The finding of dysplasia in some but not all syndromic FGPs suggests the involvement of other genes in addition to the APC gene in the development of dysplasia in FGPs.
Authors: Lucas A McDuffie; Arvind Sabesan; Michael Allgäeuer; Liqiang Xin; Christopher Koh; Theo Heller; Jeremy L Davis; Mark Raffeld; Markku Miettienen; Martha Quezado; Udo Rudloff Journal: J Clin Pathol Date: 2016-07-12 Impact factor: 3.411
Authors: Jun Li; Susan L Woods; Sue Healey; Jonathan Beesley; Xiaoqing Chen; Jason S Lee; Haran Sivakumaran; Nicci Wayte; Katia Nones; Joshua J Waterfall; John Pearson; Anne-Marie Patch; Janine Senz; Manuel A Ferreira; Pardeep Kaurah; Robertson Mackenzie; Alireza Heravi-Moussavi; Samantha Hansford; Tamsin R M Lannagan; Amanda B Spurdle; Peter T Simpson; Leonard da Silva; Sunil R Lakhani; Andrew D Clouston; Mark Bettington; Florian Grimpen; Rita A Busuttil; Natasha Di Costanzo; Alex Boussioutas; Marie Jeanjean; George Chong; Aurélie Fabre; Sylviane Olschwang; Geoffrey J Faulkner; Evangelos Bellos; Lachlan Coin; Kevin Rioux; Oliver F Bathe; Xiaogang Wen; Hilary C Martin; Deborah W Neklason; Sean R Davis; Robert L Walker; Kathleen A Calzone; Itzhak Avital; Theo Heller; Christopher Koh; Marbin Pineda; Udo Rudloff; Martha Quezado; Pavel N Pichurin; Peter J Hulick; Scott M Weissman; Anna Newlin; Wendy S Rubinstein; Jone E Sampson; Kelly Hamman; David Goldgar; Nicola Poplawski; Kerry Phillips; Lyn Schofield; Jacqueline Armstrong; Cathy Kiraly-Borri; Graeme K Suthers; David G Huntsman; William D Foulkes; Fatima Carneiro; Noralane M Lindor; Stacey L Edwards; Juliet D French; Nicola Waddell; Paul S Meltzer; Daniel L Worthley; Kasmintan A Schrader; Georgia Chenevix-Trench Journal: Am J Hum Genet Date: 2016-04-14 Impact factor: 11.025
Authors: Mazer R Ally; Ganesh R Veerappan; Corinne L Maydonovitch; Timothy J Duncan; Joseph L Perry; Eric M Osgard; Roy K H Wong Journal: Dig Dis Sci Date: 2009-10-15 Impact factor: 3.199