Activation of Hedgehog Signaling in Aggressive Hepatic Hemangioma in Newborns and Infants

Abstract

Background/aim: Hepatic hemangiomas (HH) can show an aggressive course with significant complications. Prognostic markers that identify an aggressive course are entirely absent. Since we have showed that Hedgehog signaling is overexpressed in aggressive hemangiomas of the skin. Here, we hypothesize that it is also altered in aggressive HH.

Materials and methods: Immunohistological staining for GLUT1 and quantitative PCR was performed in seven specimens with aggressive HH. For comparison, we included specimens of kaposiform hemangioendothelioma (KHE), skin hemangioma and normal liver tissue.

Results: Overexpression of the Hedgehog signaling components SHH and GLI2 and its target gene FOXA2 in HH were similar to those found in aggressive skin hemangioma and KHE, their expression being significantly higher than in mild skin hemangioma. High expression levels of SHH and FOXA2 positively correlated with HH, but not with normal liver tissue.

Conclusion: Hedgehog signaling is up-regulated in aggressive HH. This finding may lead to a biomarker allowing early intervention.

Keywords: Hepatic hemangioma; biomarkers; hedgehog signaling; infants.