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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Manuel Salto-Tellez, Institute of Cancer Research
- Second opponent: Professor Lars Andreas Akslen, University of Bergen
- Third member and chair of the evaluation committee: Professor II Anne Hansen Ree, University of Oslo
Chair of the Defence
Professor Frode Lars Jahnsen, Faculty of Medicine, University of Oslo
Principal Supervisor
Ragnhild A. Lothe, Institute of Clinical Medicine, University of Oslo
Summary
Even though colorectal cancer is one of the most common malignancies, personalized treatment lags behind other major cancer types. Adjuvant treatment following surgical resection, primarily chemotherapy, is mainly determined by tumor stage. A few biomarkers are used to select patients for targeted therapies, but only in the metastatic setting, and biomarkers are needed also in earlier stages.
Immunohistochemistry is widely used in laboratories to analyze protein expression in tissue samples. This is routinely done using the chromogenic dye DAB and the samples are scored by pathologists. The technique is valuable, but time consuming when analyzing many samples and it can be difficult to standardize. In the thesis Fluorescence-based multiplex immunohistochemistry in precision medicine of colorectal cancer Bergsland and colleagues have applied a new technology platform to study proteins by fluorescence-based multiplex immunohistochemistry combined with digital image analysis.
They first showed that the two methods provide comparable data and prognostic associations for several known biomarkers, including the protein RCC2, in a single patient series (n=922), but that digital image analysis of membrane expression could be a challenge. RCC2 was validated as a prognostic biomarker by analyzing 2000 additional tumors. Low expression of RCC2 was also found to be associated with better response to chemotherapy in stage III patients and has potential as a biomarker for selection of treatment.
Bergsland also used this new method to analyze the impact of markers in the colorectal tumor microenvironment, including regulatory T cells (Tregs). The results showed that high expression of CD25 in Tregs, as well as spatial associations between Tregs and cytotoxic T cells are both associated with poor prognosis, indicating these cells as potential targets for therapy.
Taken together, the studies of this thesis provide new strategies for personalized treatment of colorectal cancer.
Additional information
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