Advances in molecular diagnostics of hepatocellular carcinoma

Konference: 2011 7. Sympozium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Gastrointestinální nádory

Téma: Keynote lectures of invited speakers I

Číslo abstraktu: 002

Autoři: E. Pikarsky

Hepatocellular carcinoma (HCC) afflicts more than 560.000 people worldwide each year and has one of the worst 1-year survival rates of any cancer type. Currently, there are no predictive markers for finetuning treatment of patients with HCC. We found that a chromosomal region encompassing VEGF-A is amplified in a subset of HCCs in humans and mice. This subset is histologically, molecularly and biologically distinct. Moreover, human HCCs that carry a synthenic VEGF-A-amplicon, also display distinctive histological features. Expression of VEGF-A in mice amplicon bearing tumors is associated with increased blood-vessel and macrophage density, and enhanced microenvironment derived HGF expression, which can support the proliferation of the malignant cells. Accordingly, we show that these amplicon-positive tumors are uniquely sensitive to treatment with soluble VEGF-A receptor or the multi-kinase inhibitor Sorafenib, which is the first line treatment for advanced HCC. Our data indicates that cancer gene amplification may have cell-non-autonomous oncogenic effects via the tumor microenvironment. Moreover, the VEGF-A amplicon is a potential biomarker for tumor response to direct and indirect VEGF blockers. Our study underscores the potential for clinical translation of results obtained from mouse models of human cancer guided by cancer genome analysis.

Datum přednesení příspěvku: 29. 4. 2011