Case of primary cutaneous adenoid cystic carcinoma: Expression of c‐KIT and activation of its downstream signaling molecules

between low-risk and high-risk BCC. Given that IGF-1R regulates the biologic process involved in malignancy, it is possible that IGF-1R involvement explains the aggressive behavior of high-risk BCC subtypes. In addition, we suggest that IGF-1R may be a useful marker in the differentiation of high-risk BCC from low-risk BCC. We previously found nuclear IGF-1R in poorly differentiated cutaneous squamous cell carcinoma. Nuclear IGF-1R originates from the cell surface, not from an intracellular pool of newly synthesized receptors. The fact that nuclear IGF-1R binds to enhancer regions and activates transcription raises the possibility that nuclear IGF-1R may contribute to deregulated gene expression and thereby play a pathophysiological role in cancer cells. However, we did not find IGF-1R expression in the nucleus, but mainly in the membrane of tumor cells of high-risk BCC. Aberrant activation of Sonic hedgehog (Shh) signaling is considered to be a major signal transduction pathway in the BCC tumorigenesis. IGF-1 cooperates with deregulation of the Shh pathway via Akt activation. IGF-IR associate with Smo, suggesting that Shh and IGF-1 are integrated at the receptor level. Therefore, we speculate that IGF-1R may participate in the pathogenesis of high-risk BCC, although further experiments are warranted.