The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Associate Professor Kari Nielsen, Lund University, Sweden
- Second opponent: Professor Ole Didrik Lærum, University of Copenhagen, Denmark
- Third member and chair of the evaluation committee: Professor Terje Andreas Osnes, University of Oslo
Chair of the Defence
Professor Petter Gjersvik, University of Oslo
Principal Supervisor
Professor emeritus Ole Petter Fraas Clausen, University of Oslo
Summary
Keratoacanthoma (KA) is a common keratinocytic neoplasm localized to the sun-exposed skin of elderly persons. It develops rapidly during a few weeks and regresses spontaneously after a shorter or longer period of stable phase. Particularly in the early proliferative phase, it shares histological features such as infiltration and cytological atypia with the malignant cutaneous squamous cell carcinoma (cSCC) that may metastasize. Solid organ transplant recipients show an increased incidence of both KA and cSCC. Since KA and SCC have different clinical outcomes and thus require different treatments, it is essential to distinguish these tumors histopathologically. This thesis primarily aims at a better understanding of the biology of KA and also focuses on differentiating KA from cSCC in biopsies.
The thesis work is based on immunohistochemical analyses of biopsy materials and on Tp53 mutation analyses in the first article. KAs were stratified into young and old lesions according to the age given by the patients and by histopathological evaluation; the Ki 67 index was also scored.
Our first article revealed substantially higher numbers of Tp53 mutations in KA (approx. 40%) compared to results from earlier studies. Considerably higher numbers of lesions without Tp53 mutations compared to lesions with mutations in the old subgroup suggest the possible role of wild type p53 protein in the regression of KA, possibly by inducing apoptosis.
KA has a life cycle reminiscent of the hair cycle, where activation of the Wnt signaling pathway is vital for proliferation/regeneration in the anagen phase. An experimentally-induced murine KA model demonstrated an active Wnt signaling pathway in young KAs and suppression of the same pathway in old KAs. In the second article, we did not find differential expression of the Wnt signaling pathway proteins between young and old human KAs, unlike the results from the murine model.
Spindle proteins are essential for cell division, and aberrant expression of these proteins is related to carcinogenesis. In the final article, we showed a difference between KA and cSCC by demonstrating significantly higher levels of the spindle proteins Aurora-A, Mad2, and BUBR1 in cSCC compared to KA.
In summary, this thesis work has provided new insight into the development and regression of KA, and suggests that KA and cSCC are two distinct entities. Future work will focus on our international genomic research collaboration in the hope of finding possible pathways in the life cycle of KA, that may differ from cSCC.
Additional information
Contact the research support staff.