Diagnostic significance of soluble c-kit in the cerebrospinal fluid of patients with germ cell tumors

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Object. Overexpression of the protooncogene c-kit has been suggested in a gonadal germ cell tumor (GCT). Recently, the soluble isoform of c-kit (s-kit) has been expressed in a variety of cell types. The goal of this study was to investigate the expression of c-kit and the clinical significance of s-kit in patients with GCTs.

Methods. The authors first conducted an immunohistochemical investigation of the expression of the c-kit protein in 27 surgical specimens. In all 18 specimens that contained germinomas, c-kit was diffusely expressed on the cell surface of the germinoma cells, but was not found on lymphocytes or interstitial cells. In seven of eight immature teratomas, only some mature components, such as cartilage and glands, were immunoreactive for c-kit. Syncytiotrophoblastic giant cells (STGCs) demonstrated negative findings as well, suggesting that primarily germinoma cells express c-kit. Next, 47 cerebrospinal fluid (CSF) samples collected from 32 patients with GCTs (15 samples from patients with pure germinomas, 16 from patients with STGC germinomas, 14 from patients with teratomas, and two from a patient with a choriocarcinoma) were analyzed using a sandwich enzyme-linked immunosorbent assay. The level of s-kit was significantly higher in CSF collected from patients with germinomas and STGC germinomas than in CSF collected from patients with teratomas or non—germ cell brain tumors, or in CSF collected from controls. The concentration of s-kit in CSF was correlated with the patient's clinical course; it was significantly higher in pretreatment samples obtained before and in samples obtained at the time of tumor recurrence than in samples collected from patients in whom the tumor was in remission. The level of s-kit was remarkably high in CSF collected from patients with subarachnoid tumor dissemination.

Conclusions. These results indicate that the concentration of s-kit in CSF may be a useful clinical marker for germinomas, especially for detecting recurrence or subarachnoid dissemination of these lesions.

Article Information

Address reprint requests to: Hideo Takeshima, M.D., Ph.D., Department of Neurosurgery, Faculty of Medicine, Kagoshima University, 8–35–1 Sakuragaoka, Kagoshima 890–8520, Japan. email: m2040k@m3.kufm.kagoshima-u.ac.jp.

© AANS, except where prohibited by US copyright law.

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Figures

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    Photomicrographs showing immunohistochemical detection of the expression of c-kit protein in the following GCTs: germinoma (A), seminoma (B), STGC germinoma (C), choriocarcinoma (D), and teratoma (E and F). Arrows indicate STGCs that displayed a negative reaction for c-kit. Original magnifications × 100 (A, C, and D); × 50 (B and E); and × 25 (F).

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    Graph comparing levels of s-kit in 30 samples of CSF collected from patients with various histological types of GCTs. Bars and whiskers represent means ± SEMs for each group.

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    Graph comparing posttreatment CSF levels of s-kit in patients with pure germinomas and STGC germinomas. Bars and whiskers represent means ± SEMs for each subgroup.

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    Data obtained in a patient with a representative STGC germinoma. There is a correlation between the MR images and the CSF concentration of s-kit. Upper: Graph showing changes in the s-kit level from tumor onset to recurrence. Lower Left: Gadolinium-enhanced T1-weighted MR image confirming a suprasellar mass at the time of onset. Lower Center: Gadolinium-enhanced T1-weighted MR image confirming complete remission (CR) of the tumor after the patient underwent radiation therapy and chemotherapy. Lower Right: Gadolinium-enhanced T1-weighted MR image demonstrating tumor dissemination on the ventricular wall.

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