Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Angelo De Marzo, Johns Hopkins University, USA
- Second opponent: Professor Lars A. Akslen, University of Bergen,
- Third member and chair of the evaluation committee: Associate Professor Ulla Randen, University of Oslo
Chair of the Defence
Professor Kristin Austlid Tasken, University of Oslo
Principal Supervisor
Senior Consultant Ulrika Axcrona, Oslo University Hospital
Summary
Despite ongoing developments in diagnostic and prognostic tools used in prostate cancer, a substantial number of patients will still experience progression. Therefore, there is an urgent need for additional biomarkers that can identify these patients. However, the heterogeneous nature of prostate cancer on the clinical, morphological, and molecular level, complicates the implementation of new biomarkers.
In this thesis, Bogaard and colleagues aimed to identify diagnostic and prognostic biomarkers for prostate cancer by considering molecular heterogeneity and by targeting the morphological feature, cribriform pattern. They used a combination of methods, including RNA sequencing, RNA in situ hybridization, and immunohistochemistry, on a surgically treated cohort of over 500 patients.
They performed a head-to-head comparison of five promising biomarkers and demonstrated that the proliferation marker Ki-67 and a cribriform pattern were superior to the other assessed biomarkers (PTEN, ERG, and reactive stroma). The authors suggest that both biomarkers could aid in identifying patients who are more likely to experience progression, and accordingly should be included in pathology reports. Moreover, they demonstrate high levels of heterogeneity for ERG, PTEN and Ki-67 expression, underscoring the importance of multisampling in biomarker evaluation in prostate cancer.
By targeting a cribriform pattern, the authors show that Ki-67 identified a subgroup, which they named “high proliferative cribriform prostate cancer,” with a notably poor prognosis. They suggested that these patients could be candidates for additional treatment after surgery. Lastly, they identified a novel biomarker, GRIN3A, for the presence of a cribriform pattern in prostate cancer, which may serve as a diagnostic biomarker. Altogether, this thesis has contributed to identifying and developing biomarkers that could improve our approach to diagnosing and determining prognosis for prostate cancer patients.
Additional information
Contact the research support staff.