Potential immunohistochemical markers of tumor vessels in HCC

Background and objective: Antiangiogenic intervention strategies have become a major issue in modern cancer therapies. Especially in hepatocellular carcinoma (HCC) angiogenesis is of high relevance due to rich vascularisation of the tumor, early access to preexisting vascular network and high angioinvasive property. We therefore evaluated the potential for specific differentiation newly formed tumor capillaries in liver cancer.

Methods: We have used a panel of (neo-) vascularization associated markers (CD 276, CD 137, Integrin beta and Tenascin C) on paraffin tissues (Seaman et al., 2007). Slides were additionally stained against alpha smooth muscle actin (ASMA), Desmin and CD 31.

Results: Standard vascular markers (Desmin, CD 31) showed the expected staining pattern. ASMA was present in 80% of hcc tumor capillaries and all larger arterial vessels in the portal field, surrounding CD 31 positive endothelial cells but was absent arround normal or cirrhotic liver sinusoids. Among the further evaluated markers, CD 137 was expressed in some tumor cells, but not in the tumor vasculature. Integrin-beta 3 and Tenascin C did not differentiate between tumor vasculature and normal vessels. In contrast, CD 276 showed significant differences between tumor vessels and normal vasculature in all cases, where tumor vessels were present. Only 15% of portal arteries and 35% of portal veins of the surrounding liver tissue showed CD 276 expression.

Conclusion: While CD 176, Tenascin C and Integrin-beta 3 expression is neither specific nor sensitive for tumor vasculature, CD 276 and ASMA offer potential to determine tumor neoangiogenesis, although they are not absolutely specific to tumor vessels. Functional studies are needed to analyze the tumor specific regulation aspects in regard to CD 276 and ASMA expression, since they may offer potential targeting.

CD 276 - neoangiogenesis - tumor vasculature