Expression of hedgehog signaling molecules in Merkel cell carcinoma

BACKGROUND: The Hedgehog signaling pathway is important for human development and carcinogenesis in various malignancies. METHODS: One tissue microarray with triplets of 28 samples from 25 patients with Merkel cell carcinoma (MCC) was constructed. Six samples of normal skin and 5 samples of normal oral mucosa served as controls. All samples were analyzed immunohistochemically with antibodies directed against Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2, and Gli-3. RESULTS: All investigated proteins were frequently and intensely overexpressed in MCCs (Sonic hedgehog, 93%; Indian hedgehog, 84%; Patched, 86%; Smoothened, 79%; Gli-1, 79%; Gli-2, 79%; Gli-3, 86%) compared with control samples. High levels of Patched and Indian hedgehog were significantly associated with an increase in patients overall (p = .015) and recurrence-free survival (p = .011), respectively. CONCLUSIONS: Our results indicate that the Hedgehog signaling pathway is strongly activated in MCC and thus may play a role in carcinogenesis.