A review of soluble c-kit (s-kit) as a novel tumor marker and possible molecular target for the treatment of CNS germinoma.
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.
D014408:Biomarkers, Tumor / Q000032:analysis*; D016543:Central Nervous System Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D018237:Germinoma / Q000737:chemistry* / Q000188:drug therapy; D006801:Humans; D007150:Immunohistochemistry; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis* / Q000187:drug effects; D012995:Solubility
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit