PhD ceremony Mr. H. Kusano: Prognostic aspects of hepatocellurar carcinoma

PhD ceremony: Mr. H. Kusano

Dissertation: Prognostic aspects of hepatocellurar carcinoma

Promotor(s): prof. A.S.H. Gouw, prof. G Molema, prof. H. Yano

Faculty: Medical Sciences

This thesis addresses two issues that influence the prognosis of hepatocellular carcinoma (HCC), microvascular invasion (micro-VI) (part I) and interferon (IFN) therapy (part II). In a review of the current status of methods to predict micro-VI preoperatively we concluded that currently there is no reliable method to predict micro-VI before surgery. We investigated a molecular profile of micro-VI positive HCC that may yield a predictive factor of micro-VI. Results of these studies indicated the importance of peritumoral tissue as a compartment that contains changes related with micro-VI. This was represented partly in altered angiogenic characteristics as witnessed by upregulation of placental growth factor and vascular endothelial growth factor receptor-1 expression and partly in decreased numbers of ductular structures that probably undergo phenotype switching during progression of HCC as part of cancer related epithelial-mesenchymal transition. The decreasing numbers of ductules may serve as a predictive factor of micro-VI in tumour biopsies.

In part II, we evaluated pegylated IFNs (PEG-IFNs) as a promising drug combined with sorafenib. As 70% to 80% of patients with HCC are diagnosed at the advanced stage, effective systemic therapy options are still sought for. We demonstrated the anti-proliferative effect of PEG-IFNs with or without sorafenib in various HCC cell lines. Sensitivity to each combination varied leading us to conclude that molecular tumour profiling will be necessary to improve the sensitivity of therapies based on the matching of the tumour with certain drugs or combination of drugs.