Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors.

OBJECTIVE: Few molecular targets are both consistently and selectively expressed in a majority of central nervous system (CNS) neoplasms. Receptor tyrosine kinases have been implicated in brain tumor oncogenesis. We previously isolated one such receptor, discoidin domain receptor-1 (DDR1), from high-grade pediatric brain tumors. Here, we analyze the cellular origin and distribution of DDR1 expression in human brain tumors and its expression in tumor cells relative to surrounding brain. METHODS: By use of a digoxigenin-labeled DDR1 riboprobe, we investigated the expression of DDR1 messenger ribonucleic acid in a prospective series of 30 resected human primary and metastatic brain neoplasms, nonneoplastic human brain, and mouse embryonic brain, as well as a mouse glioblastoma model, by in situ hybridization. RESULTS: All the high-grade primary brain and metastatic brain tumors showed unequivocal, intense DDR1 expression within the majority of tumor cells, whereas expression was not observed in hyperplastic tumor blood vessels, normal brain blood vessels, inflammatory cells, or in the normal brain tissue that surrounded the tumor. Receptor expression was limited to tumor cells located within solid tumor tissue. Overall, 27 of 29 resected CNS tumors exhibited tumor cell-specific DDR1 expression, whereas one specimen composed of isolated glioblastoma cells within invaded brain parenchyma showed no detectable staining for this receptor. DDR1 was also expressed preferentially in the ventricular zone (a region of highly proliferating precursor cells) of mice at embryonic Day 15.5. CONCLUSION: We found that DDR1 is consistently expressed in all high-grade brain neoplasms studied and is selective for tumor cells in the specimens analyzed. The expression of DDR1 by tumor cells of CNS neoplasms and by primitive cells of the embryonic ventricular zone suggests that DDR1 is a potentially useful marker of tumor cells within the CNS.

[Dermoid cyst in the fourth ventricle associated with Klippel-Feil syndrome].

Dermoid cysts in the central nervous system are often associated with various congenital disorders, especially dermal sinus and spina bifida. We report a case of dermoid cyst in the fourth ventricle associated with Klippel-Feil syndrome. A 47-year-old man with a long history of headache had been known to have a cystic lesion in the posterior fossa for 12 years. When he was referred to our hospital with complaints of transient tetraparesis, he showed bilateral cerebellar ataxia and minimal left hemiparesis. Furthermore, he was noted to have a webbed neck with a low hairline and facial asymmetry. CT and MRI showed multiple cerebral infarctions as well as a mass lesion in the posterior fossa. Cervical roentgenogram showed a fusion of C 2 and C 3 vertebrae. The tumor was totally removed via a suboccipital approach, and the diagnosis was a dermoid cyst. The present patient had not only dermoid cyst and Klippel-Feil syndrome but also hypertrophy of the zygomatic bone. The pathogenesis of the Klippel-Feil syndrome is presumed to be an intrauterine defect, with a failure of segmentation of mesodermal somites. The zygomatic bone is also derived from the mesoderm somites at early fourth week, too. From these points of view, the disturbance in the mesoderm before the fourth week of gestation might have played an important role in causing a dermoid cyst.

[Experimental brain tumors produced transplacentally by ethylnitrosourea (IV): ultrastructure studied by using transmission and scanning electron microscope (author's transl)].

The fine structure of rat gliomas induced transplacentally with a single i.p. dose of 50 mg/kg of Ethylnitrosourea has been studied by using transmission and scanning electron microscope. The subependymal matrix layers of the fetus which was affected by ENU have showed irregular and rough arrangements with expanded extracellular spaces as compared with that of control rats. The cells of subependymal layer seemed to form the microtumor. A so-called "microtumor", which was found in a 8 week old, has been composed of small round cells. The fine structures of these cells have showed the characteristics in primitive oligodendroglioma. The characteristics of the fine structure of astrocytoma cells was identified by both TEM and SEM. The fine structure of subependymal glioma cells was often pleomorphic. These gliomas contained a mixture of primitive oligodendrocytes and ependymal cells together with anaplastic glial cells. With increasing size, the glioma has become more pleomorphic with a mixture of neoplastic oligodendrocytes, astrocytes and ependymal cells, and ependymoma like cells have showed neither cilia nor junctional complex. Abnormal vascular structure in the tumor has been reconfirmed by injection replica scanning electron microscope method. The fine structure of the separated single tumor cell surface was also studied by scanning electron microscope. The differences of the cells surface between that of astrocytoma cell and oligodendroglioma cells were clearly noticed.