The histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative study

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dc.contributor.advisorGovender, Dhirenen_ZA
dc.contributor.authorSookhayi, Raveendraen_ZA
dc.date.accessioned2015-12-09T14:44:38Z
dc.date.available2015-12-09T14:44:38Z
dc.date.issued2015en_ZA
dc.description.abstractIntroduction: It has been reported that HNPCC colorectal carcinomas demonstrate a better prognosis compared to sporadic carcinoma, however the exact mechanism for this is still uncertain. It is possible that tumour morphology, location and cell cycle markers may be indicators of the underlying molecular mechanism. In a resource limited setting these factors may help to stratify which cases need further molecular testing and genetic counselling. Aims and objectives: To characterise the macroscopic and microscopic pathology in three cohorts of patients. The cohorts include (1) patients with CRCs that are < 50 years and mutation negative, (2) < 50 years and DNA mismatch repair gene mutation positive and (3) more than 50 years (sporadic). To investigate the immunoexpression of the cell cycle regulators (p21, p27, p53, c-myc, cyclin D1 and cyclin E) and MMP-7 in each cohort. To compare the immunoexpression of each marker between cohort s. To correlate the immunoexpression of each marker with tumour type, stage and grade. Materials and methods: In total, 17 mutation negative, 15 mutation positive and 28 sporadic adenocarcinoma resection cases were available for study. The histopathological features of all cases were reviewed. The cases were stained with antibodies against p21, p27, cyclin D1, cyclin E, p53, c- myc MMP -7, MLH1, MSH2 and MSH6. Results were considered statistically significant if P < 0.05, and P <0.017 if 3 pairs of medians were compared. Results: The mutation positive tumours were more frequently right sided tumours and showed mucinous differentiation, tumour infiltrating lymphocytes and an expanding border. The sporadic and mutation negative cohort s showed similar morphology. In the sporadic cohort, the five tumours that were MLH1 negative demonstrated morphological features of MSI-H tumours. MLH1 mutations were the commonest. MLH1 immuno expression was lost in the mutation positive tumours and was statistically significant when compared to the other two cohorts. There was no statistical significance among the three cohorts for MSH2 and MSH6 immunoexpression. There was no statistically significant difference in immunoexpression for p21, p27, p53 and MMP-7 among the three cohorts. Furthermore, there was no association with tumour type and stage. Cyclin D1 expression was increased in the mutation positive cohort and was statistically significant when compared to the mutation negative cohort only. Cyclin E expression was also increased in the mutation positive cohort and was statistically significant when compared to the sporadic cohort only. Conclusion: The morphological features of colorectal carcinomas can be helpful in identifying MS I-H tumours and cases requiring further molecular studies. The cell cycle marker expression s did not explain the expected differences in patient outcome and prognosis. The mutation negative cohort in our population continues to remain enigmatic and further testing at the molecular level is required, that may reveal another novel pathway of colorectal carcinogenesis or other novel mutations in mismatch repair genes.en_ZA
dc.identifier.apacitationSookhayi, R. (2015). <i>The histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative study</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology. Retrieved from http://hdl.handle.net/11427/15734en_ZA
dc.identifier.chicagocitationSookhayi, Raveendra. <i>"The histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative study."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2015. http://hdl.handle.net/11427/15734en_ZA
dc.identifier.citationSookhayi, R. 2015. The histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative study. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Sookhayi, Raveendra AB - Introduction: It has been reported that HNPCC colorectal carcinomas demonstrate a better prognosis compared to sporadic carcinoma, however the exact mechanism for this is still uncertain. It is possible that tumour morphology, location and cell cycle markers may be indicators of the underlying molecular mechanism. In a resource limited setting these factors may help to stratify which cases need further molecular testing and genetic counselling. Aims and objectives: To characterise the macroscopic and microscopic pathology in three cohorts of patients. The cohorts include (1) patients with CRCs that are < 50 years and mutation negative, (2) < 50 years and DNA mismatch repair gene mutation positive and (3) more than 50 years (sporadic). To investigate the immunoexpression of the cell cycle regulators (p21, p27, p53, c-myc, cyclin D1 and cyclin E) and MMP-7 in each cohort. To compare the immunoexpression of each marker between cohort s. To correlate the immunoexpression of each marker with tumour type, stage and grade. Materials and methods: In total, 17 mutation negative, 15 mutation positive and 28 sporadic adenocarcinoma resection cases were available for study. The histopathological features of all cases were reviewed. The cases were stained with antibodies against p21, p27, cyclin D1, cyclin E, p53, c- myc MMP -7, MLH1, MSH2 and MSH6. Results were considered statistically significant if P < 0.05, and P <0.017 if 3 pairs of medians were compared. Results: The mutation positive tumours were more frequently right sided tumours and showed mucinous differentiation, tumour infiltrating lymphocytes and an expanding border. The sporadic and mutation negative cohort s showed similar morphology. In the sporadic cohort, the five tumours that were MLH1 negative demonstrated morphological features of MSI-H tumours. MLH1 mutations were the commonest. MLH1 immuno expression was lost in the mutation positive tumours and was statistically significant when compared to the other two cohorts. There was no statistical significance among the three cohorts for MSH2 and MSH6 immunoexpression. There was no statistically significant difference in immunoexpression for p21, p27, p53 and MMP-7 among the three cohorts. Furthermore, there was no association with tumour type and stage. Cyclin D1 expression was increased in the mutation positive cohort and was statistically significant when compared to the mutation negative cohort only. Cyclin E expression was also increased in the mutation positive cohort and was statistically significant when compared to the sporadic cohort only. Conclusion: The morphological features of colorectal carcinomas can be helpful in identifying MS I-H tumours and cases requiring further molecular studies. The cell cycle marker expression s did not explain the expected differences in patient outcome and prognosis. The mutation negative cohort in our population continues to remain enigmatic and further testing at the molecular level is required, that may reveal another novel pathway of colorectal carcinogenesis or other novel mutations in mismatch repair genes. DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - The histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative study TI - The histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative study UR - http://hdl.handle.net/11427/15734 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15734
dc.identifier.vancouvercitationSookhayi R. The histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative study. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/15734en_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.titleThe histopathology and immunohistochemical expression of cell cycle regulators and mismatch repair gene proteins in colorectal carcinoma : a comparative studyen_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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