TENASCIN-C EXPRESSION IN THE CYST WALL AND FLUID OF HUMAN BRAIN-TUMORS CORRELATES WITH ANGIOGENESIS

OBJECTIVE: Tenascin-C (TN) is an extracellular matrix glycoprotein wit h a characteristic six-armed structure. The aim of this study was to d etermine whether the concentration of TN in the cyst fluid of brain tu mors can be used as a marker for angiogenesis and glioma grade. METHOD S: We investigated the expression of TN in the cyst wall and cyst flui d of human brain tumors by immunohistochemistry, immunoprecipitation, and immunoblotting. The tumors included 12 astrocytomas (5 glioblastom a multiforme tumors, 1 anaplastic astrocytoma, 1 low-grade astrocytoma , 4 juvenile pilocytic astrocytomas, and 1 mixed glioma), 2 dysembryop lastic neuroepithelial tumors, 3 craniopharyngiomas, 2 ependymomas, 2 metastatic carcinomas, 3 arachnoid cysts, 1 glial ependymal cyst, and 1 inflammatory cyst. RESULTS: We detected no expression of TN in the c yst fluids of the ependymomas, craniopharyngiomas, and nonpilocytic lo w-grade astrocytoma. By contrast, TN was detected in the cyst fluids o f all the other tumors. Results of quantitative immunoblotting using a Phosphorlmager unit (Molecular Dynamics, Sunnyvale, CA) revealed that , on average, a 5-fold higher signal was observed in the glioblastoma multiforme tumors as compared with the anaplastic astrocytoma, and a 1 0-fold higher signal as compared with the mixed glioma, juvenile piloc ytic astrocytomas, and dysembryoplastic neuroepithelial tumors. Result s of TN immunohistochemistry in the astrocytomas correlated with gliom a grade, with stronger staining of the hyperplastic vessels and tumor cells being observed in higher grade gliomas. No TN immunoreactivity w as detected in the walls of the ependymomas, arachnoid cysts, and glia l ependymal cyst that lack hyperplastic vessels, and minimal TN immuno reactivity was observed in the perivascular gliotic rim of the craniop haryngiomas. No TN was detected in the cyst fluid of these cystic proc esses. CONCLUSION: The presence of TN in and around the hyperplastic v essels and tumor cells present in the cyst walls of astrocytomas and i ts deposition in the intratumoral cyst fluid in which angiogenic facto rs have been detected further suggests a role for TN as an angiogenic modulator. These preliminary results suggest that immunodetection of T N in the tumor cyst fluid may indicate tumor type and grade.