A review of soluble c-kit (s-kit) as a novel tumor marker and possible molecular target for the treatment of CNS germinoma.

摘要

BACKGROUND: Although germinomas are the most common central nervous system (CNS) germ cell tumors (GCTs), no specific tumor marker(s) has been identified. In the absence of such a marker, effective treatment planning requires surgical intervention to obtain a histologic diagnosis. The proto-oncogene c-kit is a transmembrane tyrosine kinase receptor that plays a crucial role in the development of germ cells and is aberrantly expressed in a variety of neoplasms. A soluble form of the c-kit (s-kit), composed of only the extracellular domain, has been identified as a functional molecule. METHODS: We immunohistochemically analyzed the distribution of c-kit to determine its expression profile in various histologic subtypes of CNS GCTs. To examine whether s-kit represents a novel clinical marker, its concentration in cerebrospinal fluid (CSF) was assayed by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: On the cell surface of germinomas, c-kit was diffusely positive. Some mature teratoma components were weakly immunoreactive for c-kit; syncytiotrophoblastic giant cells were negative. The level of s-kit was significantly higher in germinoma-containing tumors. The CSF concentration of s-kit was correlated with the clinical course; it was markedly higher in patients with subarachnoid dissemination. CONCLUSIONS: We found that s-kit could be a novel tumor marker for CNS germinomas. In addition, the diffuse expression of c-kit suggests that it may serve as a possible molecular target in the treatment of CNS germinomas.