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. (C) 2009 Wiley Periodicals, Inc. Head Neck 32: 333-340. 2010