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Adjudication committee
- First opponent: Professor Robert Harris, Karolinska Institutet, Stockholm
- Second opponent: Professor Morten Lund-Johansen, University of Bergen
- Third member and chair of the evaluation committee: Professor Mathias Toft, University of Oslo
Chair of defence
Professor Emeritus Erik Taubøll, University of Oslo
Summary
Meningiomas are the most common primary intracranial tumors in adults. While most are cured by surgical removal, up to one fifth recur, and adjuvant radiotherapy is then considered. Because such therapy carries significant side effects, accurate identification of patients at high risk of recurrence is essential. The current gold standard, the WHO histopathological classification, suffers from subjectivity and limited reproducibility.
This thesis investigated whether assessment of proliferative activity using novel immunohistochemical markers could improve recurrence prediction in human meningiomas. A retrospective cohort of 160 surgically resected meningiomas from St. Olavs Hospital was analyzed. Tissue microarrays were constructed, and tumor samples were stained for the proliferation markers PHH3, MCM7, DNA topoisomerase IIα, mitosin, survivin, and the established marker MIB-1 (Ki-67). Expression levels were quantified as the percentage of positive tumor cell nuclei among 1000 cells. Statistical analyses included ROC curves, Cox regression, and Kaplan–Meier survival analyses.
All investigated markers were expressed at significantly higher levels in WHO grade II than in grade I tumors. Recurrent tumors showed higher expression of all proliferation markers except MIB-1. PHH3, MCM7, mitosin, and survivin were independent predictors of recurrence-free survival, outperforming both WHO grade and MIB-1.
These findings demonstrate that several novel proliferation markers provide more accurate prognostic information than current histopathological grading alone. Incorporating such markers into diagnostic evaluation may refine risk stratification and help tailor postoperative follow-up and adjuvant therapy for meningioma patients.
Additional information
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