An immunohistochemical study of beta-catenin in HNPCC colon tumours

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dc.contributor.advisorHall, Pauline de la Motteen_ZA
dc.contributor.authorWatkins, Jennifer Gen_ZA
dc.date.accessioned2014-07-28T14:51:48Z
dc.date.available2014-07-28T14:51:48Z
dc.date.issued2004en_ZA
dc.descriptionIncludes bibliographical references (leaves 49-55).
dc.description.abstractBeta-catenin is normally complexed with adenomatous polyposis coli (APC) protein and E-cadherin adhesion molecule, and localized on the cell membrane. If APC/beta-catenin is disrupted, beta-catenin transfers into the nucleus, where it functions as a transcriptional activator, causing unregulated cell proliferation. The localisation of beta-catenin in H NPCC adenomas has not been studied but a shift in beta-catenin to the nucleus has been previously demonstrated in a range of col 0 recta I cancers, including those in HNPCC. The aim of the first part of the study was to determine whether there is a beta-catenin shift occurring as an early event in HNPCC tumours. Coded sections of tumours were immunohistochemically stained with antibody against beta-catenin and counterstained in haematoxylin. 14 HNPCC adenomas, 13 HNPCC carcinomas, 10 FAP adenomas, 10 FAP carcinomas, 10 sporadic adenomas and carcinomas and 10 juvenile polyps -three with dysplasia and seven without- were studied. A score was given for loss of membrane staining (0-1), presence of cytoplasmic staining (0-2) or nuclear staining (0- 2) and a total out of five obtained. An shift in beta-catenin was demonstrated at the adenoma phase in HNPCC. HNPCC, tumours were compared with sporadic tumours and a statistically significant similarity in prevalence of beta-catenin shift found in adenomas and carcinomas. The early shift in beta-catenin in HNPCC led to the second part of the study evaluating the "down-stream" effects of this shift in HNPCC tumours. TheHNPCC sections were immunohistochemically stained with E-cadherin, cmyc and cyclin 01. The results showed a positive correlation between Ecadherin loss, increased cyclin 01 and a shift in beta-catenin. No significant change in c-myc or correlation between c-myc and a shift of beta-catenin was found. In conclusion the study indicates that disruption of the APC/beta-catenin pathway plays a similar role in HNPCC tumours to that in sporadic tumours. A notable exeption is the effect on c-myc and further study is needed in this regard.en_ZA
dc.identifier.apacitationWatkins, J. G. (2004). <i>An immunohistochemical study of beta-catenin in HNPCC colon tumours</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology. Retrieved from http://hdl.handle.net/11427/3087en_ZA
dc.identifier.chicagocitationWatkins, Jennifer G. <i>"An immunohistochemical study of beta-catenin in HNPCC colon tumours."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2004. http://hdl.handle.net/11427/3087en_ZA
dc.identifier.citationWatkins, J. 2004. An immunohistochemical study of beta-catenin in HNPCC colon tumours. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Watkins, Jennifer G AB - Beta-catenin is normally complexed with adenomatous polyposis coli (APC) protein and E-cadherin adhesion molecule, and localized on the cell membrane. If APC/beta-catenin is disrupted, beta-catenin transfers into the nucleus, where it functions as a transcriptional activator, causing unregulated cell proliferation. The localisation of beta-catenin in H NPCC adenomas has not been studied but a shift in beta-catenin to the nucleus has been previously demonstrated in a range of col 0 recta I cancers, including those in HNPCC. The aim of the first part of the study was to determine whether there is a beta-catenin shift occurring as an early event in HNPCC tumours. Coded sections of tumours were immunohistochemically stained with antibody against beta-catenin and counterstained in haematoxylin. 14 HNPCC adenomas, 13 HNPCC carcinomas, 10 FAP adenomas, 10 FAP carcinomas, 10 sporadic adenomas and carcinomas and 10 juvenile polyps -three with dysplasia and seven without- were studied. A score was given for loss of membrane staining (0-1), presence of cytoplasmic staining (0-2) or nuclear staining (0- 2) and a total out of five obtained. An shift in beta-catenin was demonstrated at the adenoma phase in HNPCC. HNPCC, tumours were compared with sporadic tumours and a statistically significant similarity in prevalence of beta-catenin shift found in adenomas and carcinomas. The early shift in beta-catenin in HNPCC led to the second part of the study evaluating the "down-stream" effects of this shift in HNPCC tumours. TheHNPCC sections were immunohistochemically stained with E-cadherin, cmyc and cyclin 01. The results showed a positive correlation between Ecadherin loss, increased cyclin 01 and a shift in beta-catenin. No significant change in c-myc or correlation between c-myc and a shift of beta-catenin was found. In conclusion the study indicates that disruption of the APC/beta-catenin pathway plays a similar role in HNPCC tumours to that in sporadic tumours. A notable exeption is the effect on c-myc and further study is needed in this regard. DA - 2004 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2004 T1 - An immunohistochemical study of beta-catenin in HNPCC colon tumours TI - An immunohistochemical study of beta-catenin in HNPCC colon tumours UR - http://hdl.handle.net/11427/3087 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3087
dc.identifier.vancouvercitationWatkins JG. An immunohistochemical study of beta-catenin in HNPCC colon tumours. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2004 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3087en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Anatomical Pathologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherAnatomical Pathologyen_ZA
dc.titleAn immunohistochemical study of beta-catenin in HNPCC colon tumoursen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMMeden_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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