Tailoring Ovarian Cancer Strategies to a Sub-Saharan Region: Testing the Developed Country Experience

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dc.contributor.advisorKöbel, Martin
dc.contributor.advisorManyama, Mange J.
dc.contributor.authorRambau, Peter Fabian
dc.contributor.committeememberBenediktsson, Hallgrímur
dc.contributor.committeememberHallgrímsson, Benedikt
dc.contributor.committeememberLukowiak, Ken D.
dc.contributor.committeememberQuan, May Lynn
dc.date2018-11
dc.date.accessioned2018-08-21T15:13:20Z
dc.date.available2018-08-21T15:13:20Z
dc.date.issued2018-08-16
dc.description.abstractOvarian carcinoma is a spectrum of different histotypes which differ in risk factors, precursor lesions, molecular alterations and prognosis. Most of the research focused on high grade serous carcinoma which constitutes the majority of ovarian carcinoma. Endometrioid carcinoma (EC) constitutes 11% of ovarian carcinoma. Studies on EC have been limited by lack of sufficient number of cases for a meaningful conclusion. Seromucinous carcinoma, a newly introduced histotype shows resemblance to EC with no studies on its diagnostic reproducibility and molecular alterations. In developing countries, few studies have addressed the tumor types and histotype distribution of ovarian cancer, which could be useful in resource allocation, in addition the diagnostic accuracy of histotyping is not known. This study utilized immunohistochemical markers in a cohort of EC to study the diagnostic and prognostic biomarkers, as well as histotyping of ovarian cancers from Tanzania to establish diagnostic accuracy. Morphological studies and targeted deep sequencing was applied to seromucinous carcinoma to detect recurrent mutations known to occur in ovarian carcinoma, to justify whether it deserves a separate classification. This study found that, a defect in mismatch repair proteins was restricted to EC, and therefore screening for Lynch syndrome should be restricted to endometrioid histotype. This study also validated the association of hormone receptor (estrogen and progesterone) expression with ovarian cancer specific survival, with limited clinical utility. For seromucinous carcinoma, this study shows that the morphological diagnosis of seromucinous carcinomas is not very reliable. It did not show a distinct immunophenotype or genotype, and molecular features overlaps with endometrioid and low-grade serous carcinomas. Therefore, seromucinous carcinoma can be assigned to one of the major histotypes by ancillary molecular tests. Ovarian cancer in Tanzania shows relatively few cases compared to the Alberta population, with poor diagnostic agreement by using the current WHO criteria and immunohistochemistry. Improvement of H&E staining and adoption of current WHO classification can achieve a reasonable correct histotyping of ovarian carcinoma which can be meaningful in this area where the resource are scarce.en_US
dc.identifier.citationRambau, P. F. (2018). Tailoring Ovarian Cancer Strategies to a Sub-Saharan Region: Testing the Developed Country Experience (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32821en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/32821
dc.identifier.urihttp://hdl.handle.net/1880/107641
dc.language.isoeng
dc.publisher.facultyCumming School of Medicine
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectOvarian endometrioid carcinoma
dc.subjectdiagnostic and prognostic biomarkers
dc.subjectovarian seromucinous carcinoma
dc.subjecthistotype reproducibility
dc.subjectmolecular alterations
dc.subjectovarian cancer in Tanzania
dc.subjectovarian cancer tumor types
dc.subjectdiagnostic accuracy
dc.subject.classificationPathologyen_US
dc.titleTailoring Ovarian Cancer Strategies to a Sub-Saharan Region: Testing the Developed Country Experience
dc.typedoctoral thesis
thesis.degree.disciplineMedical Science
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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