Occurrence of a glioblastoma-associated Tenascin-C isoform in cerebral cavernomas and neighboring vessels

OBJECTIVE: Regrowth of cerebral cavernomas after apparently complete excision, de novo occurrence, and evidence of proliferation-related patterns raise the question as to their intrinsic growth potential. A particular isoform (Type III repeat c) of the glycoprotein tenascin-C (TN-C), typically associated with the vessels of anaplastic gliomas, is regarded as a marker of vascular proliferation in lesions growing within brain tissue. This study sought to ascertain whether this isoform is expressed in cerebral cavernomas to gain further insight into the growth potential of these lesions. METHODS: Sixteen cerebral cavernomas and three fragments of normal brain underwent immunohistochemical examinations via two antibody fragments obtained by phage display technology. Previous characterization demonstrated that the fragment TN-12 recognizes the epidermal growth factor-like repeat, common to all TN-C isoforms. On the contrary, the fragment TN-11 was found to be highly specific for the Type III repeat c isoform. RESULTS: Accumulation of total TN-C was found in the vascular walls and in the interspaces between the blood cavities of all examined cavernomas. When the antibody fragment TN-11 was used, staining of the subendothelial layers occurred in both the bulk of the cavernomas and vessels of the white matter surrounding the lesions, but staining was absent in the control specimens. CONCLUSION: The distribution of the Type III repeat c isoform of TN-C, a putative marker of vascular proliferation, within cerebral cavernomas is consistent with the hypothesis of a growth potential of cerebral cavernomas. Enlargement of these lesions might involve recruitment of neighboring vasculature, which is possibly dependent on environmental conditions.